Transplant

In a clinical trial comparing three graft-versus-host disease (GVHD)–prevention regimens in patients undergoing hematopoietic stem cell transplants, a calcineurin inhibitor (CNI)–free strategy using CD34-selected peripheral blood stem cells (PBSCs) was associated with a nearly twofold increase in transplant-related mortality, compared with either a different CNI-free regimen or tacrolimus plus methotrexate, investigators reported.

In the phase 3 Progress II trial, patients who received CD34-selected PBSCs without post-transplant immune suppression had a hazard ratio for death of 1.74 compared with patients who received T-cell depletion with posttransplant cyclophosphamide, and a HR of 1.78, compared with patients who received tacrolimus and methotrexate after a bone marrow graft, Miguel-Angel Perales , MD, from Memorial Sloan Kettering Cancer Center, New York, reported at the Transplant & Cellular Therapies Meetings.

“CD34 selection was associated with worse overall survival, which offset any benefit from lower rates of moderate to severe chronic GVHD,” he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Neither of the two CNI-free interventions were superior to tacrolimus/methotrexate with bone marrow–derived stem cells for preventing chronic GVHD, and there were no differences in the primary endpoint of chronic GVHD/relapse-free survival, Dr. Perales said.
 

T-cell depletion vs. CNI

The Progress II trial was designed to see whether either of two CNI-free, T-cell depletion approaches could improve chronic GVHD rates post transplant over a CNI-based regimen.

The investigators enrolled patients aged 65 years or younger with acute leukemia or myelodysplasia with fewer than 5% blasts and a HLA-matched related or unrelated donor.

The patients were randomly assigned to either bone marrow grafts with tacrolimus/methotrexate (118 patients), bone marrow with in vivo posttransplant cyclophosphamide (114), or PBSCs with ex vivo CD34-selected cells (114).

The primary endpoint of chronic GVHD/relapse-free survival (CRFS) was a time-to-event outcome defined as moderate to severe chronic GVHD according to National Institutes of Health consensus criteria, disease relapse or progression, or death from any cause.

As noted before, there were no between-arm differences in the primary CRFS endpoint, and in multivariate analysis controlling for donor type, patient characteristics, disease category and disease risk index, the only factor significantly predictive for CRFS was being aged 50 years or older.

The 2-year posttransplant survival rates were 61.6% in the CD34-selected arm, 76.7% in the posttransplant cyclophosphamide arm, and 74.2% in the tacrolimus/methotrexate arm.

As noted before, the HR for CRFS with CD34 versus tacrolimus/methotrexate was 1.74, and for CD34 versus cyclophosphamide was 1.78 (P = .02 for both comparisons). In contrast, there was no differe­nce in CRFS between posttransplant cyclophosphamide and tacrolimus/methotrexate.

Both relapse-free survival and transplant-related mortality were worse with the CD34-selected group, compared with the other two groups, but there were no significant differences among the arms in disease relapse.

Hematologic recovery was faster in the CD34 arm, but there were no significant differences in graft failure.

In addition, the incidence of grade II-IV acute GVHD was increased in the posttransplant cyclophosphamide group, compared with the other two, while chronic GVHD and moderate to severe chronic GVHD were reduced in the CD34 group.

There were no differences in quality of life measures among the groups, Dr. Perales said.
 

Practice changing?

In the question-and answer-session following the presentation, comoderator Sarah Nikiforow , MD, PhD, from the Dana-Farber Cancer Institute in Boston, who was not involved in the study, asked whether the trial results could be considered as practice changing for any centers that historically have done CD34 selection, or whether CD34 selection is still a viable approach to GVHD prophylaxis.

“That’s obviously a key question from the study, and a question that we’re asking ourselves,” Dr. Perales said. “I think the lesson that we took from this study as it pertains to CD34 selection is obviously the increased mortality, likely related to regimen toxicity, and I think the use of high-dose radiation is something that we have to reexamine.”

He said that his center is also considering whether to reduce antithymocyte globulin dosing, move it earlier in the process, and to use pharmokinetic-directed ATG as a possible means of decreasing nonrelapse mortality.

“I think it remains a useful platform for adoptive cell therapy, potentially targeting relapsed disease,” he added.

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Perales disclosed advisory board activities and consulting for multiple companies, and receiving research funding for clinical trials from several more. Dr. Nikiforow disclosed a consulting/advisory role for Kite Pharma, and travel accommodations and expense from Celyad Oncology.

In a clinical trial comparing three graft-versus-host disease (GVHD)–prevention regimens in patients undergoing hematopoietic stem cell transplants, a calcineurin inhibitor (CNI)–free strategy using CD34-selected peripheral blood stem cells (PBSCs) was associated with a nearly twofold increase in transplant-related mortality, compared with either a different CNI-free regimen or tacrolimus plus methotrexate, investigators reported.

In the phase 3 Progress II trial, patients who received CD34-selected PBSCs without post-transplant immune suppression had a hazard ratio for death of 1.74 compared with patients who received T-cell depletion with posttransplant cyclophosphamide, and a HR of 1.78, compared with patients who received tacrolimus and methotrexate after a bone marrow graft, Miguel-Angel Perales , MD, from Memorial Sloan Kettering Cancer Center, New York, reported at the Transplant & Cellular Therapies Meetings.

“CD34 selection was associated with worse overall survival, which offset any benefit from lower rates of moderate to severe chronic GVHD,” he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Neither of the two CNI-free interventions were superior to tacrolimus/methotrexate with bone marrow–derived stem cells for preventing chronic GVHD, and there were no differences in the primary endpoint of chronic GVHD/relapse-free survival, Dr. Perales said.
 

T-cell depletion vs. CNI

The Progress II trial was designed to see whether either of two CNI-free, T-cell depletion approaches could improve chronic GVHD rates post transplant over a CNI-based regimen.

The investigators enrolled patients aged 65 years or younger with acute leukemia or myelodysplasia with fewer than 5% blasts and a HLA-matched related or unrelated donor.

The patients were randomly assigned to either bone marrow grafts with tacrolimus/methotrexate (118 patients), bone marrow with in vivo posttransplant cyclophosphamide (114), or PBSCs with ex vivo CD34-selected cells (114).

The primary endpoint of chronic GVHD/relapse-free survival (CRFS) was a time-to-event outcome defined as moderate to severe chronic GVHD according to National Institutes of Health consensus criteria, disease relapse or progression, or death from any cause.

As noted before, there were no between-arm differences in the primary CRFS endpoint, and in multivariate analysis controlling for donor type, patient characteristics, disease category and disease risk index, the only factor significantly predictive for CRFS was being aged 50 years or older.

The 2-year posttransplant survival rates were 61.6% in the CD34-selected arm, 76.7% in the posttransplant cyclophosphamide arm, and 74.2% in the tacrolimus/methotrexate arm.

As noted before, the HR for CRFS with CD34 versus tacrolimus/methotrexate was 1.74, and for CD34 versus cyclophosphamide was 1.78 (P = .02 for both comparisons). In contrast, there was no differe­nce in CRFS between posttransplant cyclophosphamide and tacrolimus/methotrexate.

Both relapse-free survival and transplant-related mortality were worse with the CD34-selected group, compared with the other two groups, but there were no significant differences among the arms in disease relapse.

Hematologic recovery was faster in the CD34 arm, but there were no significant differences in graft failure.

In addition, the incidence of grade II-IV acute GVHD was increased in the posttransplant cyclophosphamide group, compared with the other two, while chronic GVHD and moderate to severe chronic GVHD were reduced in the CD34 group.

There were no differences in quality of life measures among the groups, Dr. Perales said.
 

Practice changing?

In the question-and answer-session following the presentation, comoderator Sarah Nikiforow , MD, PhD, from the Dana-Farber Cancer Institute in Boston, who was not involved in the study, asked whether the trial results could be considered as practice changing for any centers that historically have done CD34 selection, or whether CD34 selection is still a viable approach to GVHD prophylaxis.

“That’s obviously a key question from the study, and a question that we’re asking ourselves,” Dr. Perales said. “I think the lesson that we took from this study as it pertains to CD34 selection is obviously the increased mortality, likely related to regimen toxicity, and I think the use of high-dose radiation is something that we have to reexamine.”

He said that his center is also considering whether to reduce antithymocyte globulin dosing, move it earlier in the process, and to use pharmokinetic-directed ATG as a possible means of decreasing nonrelapse mortality.

“I think it remains a useful platform for adoptive cell therapy, potentially targeting relapsed disease,” he added.

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Perales disclosed advisory board activities and consulting for multiple companies, and receiving research funding for clinical trials from several more. Dr. Nikiforow disclosed a consulting/advisory role for Kite Pharma, and travel accommodations and expense from Celyad Oncology.

In a clinical trial comparing three graft-versus-host disease (GVHD)–prevention regimens in patients undergoing hematopoietic stem cell transplants, a calcineurin inhibitor (CNI)–free strategy using CD34-selected peripheral blood stem cells (PBSCs) was associated with a nearly twofold increase in transplant-related mortality, compared with either a different CNI-free regimen or tacrolimus plus methotrexate, investigators reported.

In the phase 3 Progress II trial, patients who received CD34-selected PBSCs without post-transplant immune suppression had a hazard ratio for death of 1.74 compared with patients who received T-cell depletion with posttransplant cyclophosphamide, and a HR of 1.78, compared with patients who received tacrolimus and methotrexate after a bone marrow graft, Miguel-Angel Perales , MD, from Memorial Sloan Kettering Cancer Center, New York, reported at the Transplant & Cellular Therapies Meetings.

“CD34 selection was associated with worse overall survival, which offset any benefit from lower rates of moderate to severe chronic GVHD,” he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Neither of the two CNI-free interventions were superior to tacrolimus/methotrexate with bone marrow–derived stem cells for preventing chronic GVHD, and there were no differences in the primary endpoint of chronic GVHD/relapse-free survival, Dr. Perales said.
 

T-cell depletion vs. CNI

The Progress II trial was designed to see whether either of two CNI-free, T-cell depletion approaches could improve chronic GVHD rates post transplant over a CNI-based regimen.

The investigators enrolled patients aged 65 years or younger with acute leukemia or myelodysplasia with fewer than 5% blasts and a HLA-matched related or unrelated donor.

The patients were randomly assigned to either bone marrow grafts with tacrolimus/methotrexate (118 patients), bone marrow with in vivo posttransplant cyclophosphamide (114), or PBSCs with ex vivo CD34-selected cells (114).

The primary endpoint of chronic GVHD/relapse-free survival (CRFS) was a time-to-event outcome defined as moderate to severe chronic GVHD according to National Institutes of Health consensus criteria, disease relapse or progression, or death from any cause.

As noted before, there were no between-arm differences in the primary CRFS endpoint, and in multivariate analysis controlling for donor type, patient characteristics, disease category and disease risk index, the only factor significantly predictive for CRFS was being aged 50 years or older.

The 2-year posttransplant survival rates were 61.6% in the CD34-selected arm, 76.7% in the posttransplant cyclophosphamide arm, and 74.2% in the tacrolimus/methotrexate arm.

As noted before, the HR for CRFS with CD34 versus tacrolimus/methotrexate was 1.74, and for CD34 versus cyclophosphamide was 1.78 (P = .02 for both comparisons). In contrast, there was no differe­nce in CRFS between posttransplant cyclophosphamide and tacrolimus/methotrexate.

Both relapse-free survival and transplant-related mortality were worse with the CD34-selected group, compared with the other two groups, but there were no significant differences among the arms in disease relapse.

Hematologic recovery was faster in the CD34 arm, but there were no significant differences in graft failure.

In addition, the incidence of grade II-IV acute GVHD was increased in the posttransplant cyclophosphamide group, compared with the other two, while chronic GVHD and moderate to severe chronic GVHD were reduced in the CD34 group.

There were no differences in quality of life measures among the groups, Dr. Perales said.
 

Practice changing?

In the question-and answer-session following the presentation, comoderator Sarah Nikiforow , MD, PhD, from the Dana-Farber Cancer Institute in Boston, who was not involved in the study, asked whether the trial results could be considered as practice changing for any centers that historically have done CD34 selection, or whether CD34 selection is still a viable approach to GVHD prophylaxis.

“That’s obviously a key question from the study, and a question that we’re asking ourselves,” Dr. Perales said. “I think the lesson that we took from this study as it pertains to CD34 selection is obviously the increased mortality, likely related to regimen toxicity, and I think the use of high-dose radiation is something that we have to reexamine.”

He said that his center is also considering whether to reduce antithymocyte globulin dosing, move it earlier in the process, and to use pharmokinetic-directed ATG as a possible means of decreasing nonrelapse mortality.

“I think it remains a useful platform for adoptive cell therapy, potentially targeting relapsed disease,” he added.

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Perales disclosed advisory board activities and consulting for multiple companies, and receiving research funding for clinical trials from several more. Dr. Nikiforow disclosed a consulting/advisory role for Kite Pharma, and travel accommodations and expense from Celyad Oncology.

Steroids are usually the first choice of therapy for the treatment of patients with graft-vs.-host disease (GVHD), but complications from steroid use may carry a high financial cost, investigators caution.

Among 689 patients with a diagnosis of GVHD following a hematopoietic stem cell transplant (HSCT) who received steroids, 685 (97%) had at least one steroid-related complication, resulting in nearly $165,000 in mean health-care costs over 24 months, said Elizabeth J. Bell, PhD, MPH, an epidemiologist at Optum Inc.

“For both acute and chronic GVHD, the standard of care for first-line treatment is systemic steroids. The complications associated with steroid treatment are well known. However, the health-care resources utilized and the costs incurred by these patients are not well-quantified,” she said at the Transplantation & Cellular Therapies Meetings (Abstract 12).

Dr. Bell reported the results of a retrospective database analysis on costs associated with steroid complications in HSCT recipients at the meeting, which was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

She and colleagues from Optum, Incyte, and the University of Minnesota in Minneapolis looked at data on 689 patients with a diagnosis of GVHD after HSCT who received systemic steroids from July 1, 2010, through Aug. 31, 2019. The data were extracted from the Optum Research database, and included U.S. commercial and Medicare Advantage patients.

They looked at total complications and steroid-associated complications in each of four categories: infections; metabolic or endocrine complications (for example, diabetes, dyslipidemia); gastrointestinal (GI) complications (e.g., peptic ulcer disease); and bone or muscle complications (myopathy, etc).

They estimated costs based on International Classification of Diseases (ICD) codes for any steroid complications during the 24 months after steroid initiation, including those complications that may have been present at the time of GVHD diagnosis.

The median patient age was 55 years, and 60% of the sample were male. The mean Charlson Comorbidity Index score at baseline was 3.

Overall, 22% of patients had only acute GVHD, 21% had only chronic GVHD, and 39% had both acute and chronic disease. The GVHD type was unspecified in the remaining 18%.

The median time from GVHD diagnosis to initiating steroids was 30 days for patients with both acute and chronic disease, as well as those with both presentations. The median time to initiation was 36 days for patients with unspecified GVHD type.

The median cumulative duration of steroid use over 24 months was 62 days for patients with acute GVHD, 208 days for those with chronic GVHD, 166 days for those with both, and 74 days for patients with unspecified GVHD type.

As noted before, complications occurred in 97% of patients, with infections being the most common complications, occurring in 80% of patients, followed by metabolic/endocrine complications in 32%, gastrointestinal in 29%, and bone/muscle complications in 20%.

For the 665 patients who had any steroid-related complication, the mean costs of steroid-associated care in the 24 months after they were started on steroids was $164,787, and the median cost was $50,834.

Health care costs were highest among patients with infections, at a mean of $167,473, and a median of $57,680, followed by bone/muscle conditions ($75,289 and $2,057, respectively), GI conditions ($67,861 and $3,360), and metabolic or endocrine conditions ($47, 101 and $1,164).

In all categories, hospitalizations accounted for the large majority of costs.

Two-thirds (66%) of patients who experienced any steroid-related complication required hospitalization, primarily for infections.

Among all patients with complications, the median cumulative hospital stay over 24 months was 20 days, with bone/muscle complications and infections associated with a median of 19 and 18 days of hospitalization, respectively.

Dr. Bell acknowledged that the study was limited by use of ICD coding to identify steroid complication-related health-care utilization and costs, which can be imprecise, and by the fact that the analysis included only complications resulting in health care use as documented in medical claims. In addition, the investigators noted that they could not control for the possibility that steroids exacerbated conditions that existed at baseline.

“These findings emphasize the need to cautiously evaluate the treatment options for patients with GVHD. Future study with medical records is needed to provide insights on the clinical aspects of the complications (e.g., severity and suspected causality),” Dr. Bell and colleagues concluded in the study’s abstract.
 

Definitions questioned

An HSCT specialist approached for comment said that the findings of the study made sense, but she had questions regarding the study methodology.

“I would intuitively think that steroid-associated complications are a major cause of health care use in GVHD patients and it’s interesting to see that there is emerging data to support this hypothesis,” HSCT specialist Hélène Schoemans, MD of the University of Leuven, Belgium, said in an interview.

She noted, however, that “it is surprising that the period of steroid initiation was the same for acute and chronic GVHD,” and questioned whether that anomalous finding could be due to the study’s definition of acute and chronic GVHD or to how the period from baseline to steroid initiation was defined.

The questions about the definitions and timing of therapy make it uncertain as to whether the complications reported were caused by steroids or by some other factor, she suggested.

The study was supported by Optum Inc. Dr. Bell is an employee of the company, and a paid consultant of Incyte. Dr. Schoemans has received travel expenses from Celgene, Abbvie, and Incyte; is part of the advisory boards for Incyte; and has received speakers fees from Novartis, Incyte, Jazz Pharmaceuticals, and Takeda.

Steroids are usually the first choice of therapy for the treatment of patients with graft-vs.-host disease (GVHD), but complications from steroid use may carry a high financial cost, investigators caution.

Among 689 patients with a diagnosis of GVHD following a hematopoietic stem cell transplant (HSCT) who received steroids, 685 (97%) had at least one steroid-related complication, resulting in nearly $165,000 in mean health-care costs over 24 months, said Elizabeth J. Bell, PhD, MPH, an epidemiologist at Optum Inc.

“For both acute and chronic GVHD, the standard of care for first-line treatment is systemic steroids. The complications associated with steroid treatment are well known. However, the health-care resources utilized and the costs incurred by these patients are not well-quantified,” she said at the Transplantation & Cellular Therapies Meetings (Abstract 12).

Dr. Bell reported the results of a retrospective database analysis on costs associated with steroid complications in HSCT recipients at the meeting, which was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

She and colleagues from Optum, Incyte, and the University of Minnesota in Minneapolis looked at data on 689 patients with a diagnosis of GVHD after HSCT who received systemic steroids from July 1, 2010, through Aug. 31, 2019. The data were extracted from the Optum Research database, and included U.S. commercial and Medicare Advantage patients.

They looked at total complications and steroid-associated complications in each of four categories: infections; metabolic or endocrine complications (for example, diabetes, dyslipidemia); gastrointestinal (GI) complications (e.g., peptic ulcer disease); and bone or muscle complications (myopathy, etc).

They estimated costs based on International Classification of Diseases (ICD) codes for any steroid complications during the 24 months after steroid initiation, including those complications that may have been present at the time of GVHD diagnosis.

The median patient age was 55 years, and 60% of the sample were male. The mean Charlson Comorbidity Index score at baseline was 3.

Overall, 22% of patients had only acute GVHD, 21% had only chronic GVHD, and 39% had both acute and chronic disease. The GVHD type was unspecified in the remaining 18%.

The median time from GVHD diagnosis to initiating steroids was 30 days for patients with both acute and chronic disease, as well as those with both presentations. The median time to initiation was 36 days for patients with unspecified GVHD type.

The median cumulative duration of steroid use over 24 months was 62 days for patients with acute GVHD, 208 days for those with chronic GVHD, 166 days for those with both, and 74 days for patients with unspecified GVHD type.

As noted before, complications occurred in 97% of patients, with infections being the most common complications, occurring in 80% of patients, followed by metabolic/endocrine complications in 32%, gastrointestinal in 29%, and bone/muscle complications in 20%.

For the 665 patients who had any steroid-related complication, the mean costs of steroid-associated care in the 24 months after they were started on steroids was $164,787, and the median cost was $50,834.

Health care costs were highest among patients with infections, at a mean of $167,473, and a median of $57,680, followed by bone/muscle conditions ($75,289 and $2,057, respectively), GI conditions ($67,861 and $3,360), and metabolic or endocrine conditions ($47, 101 and $1,164).

In all categories, hospitalizations accounted for the large majority of costs.

Two-thirds (66%) of patients who experienced any steroid-related complication required hospitalization, primarily for infections.

Among all patients with complications, the median cumulative hospital stay over 24 months was 20 days, with bone/muscle complications and infections associated with a median of 19 and 18 days of hospitalization, respectively.

Dr. Bell acknowledged that the study was limited by use of ICD coding to identify steroid complication-related health-care utilization and costs, which can be imprecise, and by the fact that the analysis included only complications resulting in health care use as documented in medical claims. In addition, the investigators noted that they could not control for the possibility that steroids exacerbated conditions that existed at baseline.

“These findings emphasize the need to cautiously evaluate the treatment options for patients with GVHD. Future study with medical records is needed to provide insights on the clinical aspects of the complications (e.g., severity and suspected causality),” Dr. Bell and colleagues concluded in the study’s abstract.
 

Definitions questioned

An HSCT specialist approached for comment said that the findings of the study made sense, but she had questions regarding the study methodology.

“I would intuitively think that steroid-associated complications are a major cause of health care use in GVHD patients and it’s interesting to see that there is emerging data to support this hypothesis,” HSCT specialist Hélène Schoemans, MD of the University of Leuven, Belgium, said in an interview.

She noted, however, that “it is surprising that the period of steroid initiation was the same for acute and chronic GVHD,” and questioned whether that anomalous finding could be due to the study’s definition of acute and chronic GVHD or to how the period from baseline to steroid initiation was defined.

The questions about the definitions and timing of therapy make it uncertain as to whether the complications reported were caused by steroids or by some other factor, she suggested.

The study was supported by Optum Inc. Dr. Bell is an employee of the company, and a paid consultant of Incyte. Dr. Schoemans has received travel expenses from Celgene, Abbvie, and Incyte; is part of the advisory boards for Incyte; and has received speakers fees from Novartis, Incyte, Jazz Pharmaceuticals, and Takeda.

Steroids are usually the first choice of therapy for the treatment of patients with graft-vs.-host disease (GVHD), but complications from steroid use may carry a high financial cost, investigators caution.

Among 689 patients with a diagnosis of GVHD following a hematopoietic stem cell transplant (HSCT) who received steroids, 685 (97%) had at least one steroid-related complication, resulting in nearly $165,000 in mean health-care costs over 24 months, said Elizabeth J. Bell, PhD, MPH, an epidemiologist at Optum Inc.

“For both acute and chronic GVHD, the standard of care for first-line treatment is systemic steroids. The complications associated with steroid treatment are well known. However, the health-care resources utilized and the costs incurred by these patients are not well-quantified,” she said at the Transplantation & Cellular Therapies Meetings (Abstract 12).

Dr. Bell reported the results of a retrospective database analysis on costs associated with steroid complications in HSCT recipients at the meeting, which was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

She and colleagues from Optum, Incyte, and the University of Minnesota in Minneapolis looked at data on 689 patients with a diagnosis of GVHD after HSCT who received systemic steroids from July 1, 2010, through Aug. 31, 2019. The data were extracted from the Optum Research database, and included U.S. commercial and Medicare Advantage patients.

They looked at total complications and steroid-associated complications in each of four categories: infections; metabolic or endocrine complications (for example, diabetes, dyslipidemia); gastrointestinal (GI) complications (e.g., peptic ulcer disease); and bone or muscle complications (myopathy, etc).

They estimated costs based on International Classification of Diseases (ICD) codes for any steroid complications during the 24 months after steroid initiation, including those complications that may have been present at the time of GVHD diagnosis.

The median patient age was 55 years, and 60% of the sample were male. The mean Charlson Comorbidity Index score at baseline was 3.

Overall, 22% of patients had only acute GVHD, 21% had only chronic GVHD, and 39% had both acute and chronic disease. The GVHD type was unspecified in the remaining 18%.

The median time from GVHD diagnosis to initiating steroids was 30 days for patients with both acute and chronic disease, as well as those with both presentations. The median time to initiation was 36 days for patients with unspecified GVHD type.

The median cumulative duration of steroid use over 24 months was 62 days for patients with acute GVHD, 208 days for those with chronic GVHD, 166 days for those with both, and 74 days for patients with unspecified GVHD type.

As noted before, complications occurred in 97% of patients, with infections being the most common complications, occurring in 80% of patients, followed by metabolic/endocrine complications in 32%, gastrointestinal in 29%, and bone/muscle complications in 20%.

For the 665 patients who had any steroid-related complication, the mean costs of steroid-associated care in the 24 months after they were started on steroids was $164,787, and the median cost was $50,834.

Health care costs were highest among patients with infections, at a mean of $167,473, and a median of $57,680, followed by bone/muscle conditions ($75,289 and $2,057, respectively), GI conditions ($67,861 and $3,360), and metabolic or endocrine conditions ($47, 101 and $1,164).

In all categories, hospitalizations accounted for the large majority of costs.

Two-thirds (66%) of patients who experienced any steroid-related complication required hospitalization, primarily for infections.

Among all patients with complications, the median cumulative hospital stay over 24 months was 20 days, with bone/muscle complications and infections associated with a median of 19 and 18 days of hospitalization, respectively.

Dr. Bell acknowledged that the study was limited by use of ICD coding to identify steroid complication-related health-care utilization and costs, which can be imprecise, and by the fact that the analysis included only complications resulting in health care use as documented in medical claims. In addition, the investigators noted that they could not control for the possibility that steroids exacerbated conditions that existed at baseline.

“These findings emphasize the need to cautiously evaluate the treatment options for patients with GVHD. Future study with medical records is needed to provide insights on the clinical aspects of the complications (e.g., severity and suspected causality),” Dr. Bell and colleagues concluded in the study’s abstract.
 

Definitions questioned

An HSCT specialist approached for comment said that the findings of the study made sense, but she had questions regarding the study methodology.

“I would intuitively think that steroid-associated complications are a major cause of health care use in GVHD patients and it’s interesting to see that there is emerging data to support this hypothesis,” HSCT specialist Hélène Schoemans, MD of the University of Leuven, Belgium, said in an interview.

She noted, however, that “it is surprising that the period of steroid initiation was the same for acute and chronic GVHD,” and questioned whether that anomalous finding could be due to the study’s definition of acute and chronic GVHD or to how the period from baseline to steroid initiation was defined.

The questions about the definitions and timing of therapy make it uncertain as to whether the complications reported were caused by steroids or by some other factor, she suggested.

The study was supported by Optum Inc. Dr. Bell is an employee of the company, and a paid consultant of Incyte. Dr. Schoemans has received travel expenses from Celgene, Abbvie, and Incyte; is part of the advisory boards for Incyte; and has received speakers fees from Novartis, Incyte, Jazz Pharmaceuticals, and Takeda.

Despite improvements in prevention of graft-versus-host disease, chronic GVHD still occurs in 10%-50% of patients who undergo an allogeneic hematopoietic stem cell transplant, and these patients may require prolonged treatment with multiple lines of therapy, said a hematologist and transplant researcher.

“More effective, less toxic therapies for chronic GVHD are needed,” Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Research Center in Seattle said at the Transplant & Cellular Therapies Meetings.

Dr. Lee reviewed clinical trials for chronic GVHD at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Although the incidence of chronic GVHD has gradually declined over the last 40 years and both relapse-free and overall survival following a chronic GVHD diagnosis have improved, “for patients who are diagnosed with chronic GVHD, they still will see many lines of therapy and many years of therapy,” she said.

Among 148 patients with chronic GVHD treated at her center, for example, 66% went on to two lines of therapy, 50% went on to three lines, 37% required four lines of therapy, and 20% needed five lines or more.

Salvage therapies for patients with chronic GVHD have evolved away from immunomodulators and immunosuppressants in the early 1990s, toward monoclonal antibodies such as rituximab in the early 2000s, to interleukin-2 and to tyrosine kinase inhibitors such as ruxolitinib (Jakafi) and ibrutinib (Imbruvica).

There are currently 36 agents that are FDA approved for at least one indication and can also be prescribed for the treatment of chronic GVHD, Dr. Lee noted.
 

Treatment goals

Dr. Lee laid out six goals for treating patients with chronic GVHD. They include:

• Controlling current signs and symptoms, measured by response rates and patient-reported outcomes
• Preventing further tissue and organ damage
• Minimizing toxicity
• Maintaining graft-versus-tumor effect
• Achieving graft tolerance and stopping immunosuppression
• Decreasing nonrelapse mortality and improving survival

Active trials

Dr. Lee identified 33 trials with chronic GVHD as an indication that are currently recruiting, and an additional 13 trials that are active but closed to recruiting. The trials can be generally grouped by mechanism of action, and involve agents targeting T-regulatory cells, B cells and/or B-cell receptor (BCR) signaling, monocytes/macrophages, costimulatory blockage, a proteasome inhibition, Janus kinase (JAK) 1/2 inhibitors, ROCK2 inhibitors, hedgehog pathway inhibition, cellular therapy, and organ-targeted therapy.

Most of the trials have overall response rate as the primary endpoint, and all but five are currently in phase 1 or 2. The currently active phase 3 trials include two with ibrutinib, one with the investigational agent itacitinib, one with ruxolitinib, and one with mesenchymal stem cells.

“I’ll note that, when results are reported, the denominator really matters for the overall response rate, especially if you’re talking about small trials, because if you require the patient to be treated with an agent for a certain period of time, and you take out all the people who didn’t make it to that time point, then your overall response rate looks better,” she said.
 

BTK inhibitors

The first-in-class Bruton tyrosine kinase (BTK) inhibitor ibrutinib was the first and thus far only agent approved by the Food and Drug Administration for chronic GVHD. The approval was based on a single-arm, multicenter trial with 42 patients.

The ORR in this trial was 69%, consisting of 31% complete responses and 38% partial responses, with a duration of response longer than 10 months in slightly more than half of all patients. In all, 24% of patients had improvement of symptoms in two consecutive visits, and 29% continued on ibrutinib at the time of the primary analysis in 2017.

Based on these promising results, acalabrutinib, which is more potent and selective for BTK than ibrutinib, with no effect on either platelets or natural killer cells, is currently under investigation in a phase 2 trial in 50 patients at a dose of 100 mg orally twice daily.
 

JAK1/2 inhibition

The JAK1 inhibitor itacitinib failed to meet its primary ORR endpoint in the phase 3 GRAVITAS-301 study, according to a press release, but the manufacturer (Incyte) said that it is continuing its commitment to JAK inhibitors with ruxolitinib, which has shown activity against acute, steroid-refractory GVHD, and is being explored for prevention of chronic GVHD in the randomized, phase 3 REACH3 study.

The trial met its primary endpoint for a higher ORR at week 24 with ruxolitinib versus best available therapy, at 49.7% versus 25.6%, respectively, which translated into an odds ratio for response with the JAK inhibitor of 2.99 (P < .0001).
 

Selective T-cell expansion

Efavaleukin alfa is an IL-2-mutated protein (mutein), with a mutation in the IL-2RB-binding portion of IL-2 causing increased selectivity for regulatory T-cell expansion. It is bound to an IgG-Fc domain that is itself mutated, with reduced Fc receptor binding and IgG effector function to give it a longer half life. This agent is being studied in a phase 1/2 trial in a subcutaneous formulation delivered every 1 or 2 weeks to 68 patients.

Monocyte/macrophage depletion

Axatilimab is a high-affinity antibody targeting colony stimulating factor–1 receptor (CSF-1R) expressed on monocytes and macrophages. By blocking CSF-1R, it depletes circulation of nonclassical monocytes and prevents the differentiation and survival of M2 macrophages in tissue.

It is currently being investigated 30 patients in a phase 1/2 study in an intravenous formulation delivered over 30 minutes every 2-4 weeks.
 

Hedgehog pathway inhibition

There is evidence suggesting that hedgehog pathway inhibition can lessen fibrosis. Glasdegib (Daurismo) a potent selective oral inhibitor of the hedgehog signaling pathway, is approved for use with low-dose cytarabine for patients with newly diagnosed acute myeloid leukemia aged older than 75 years or have comorbidities precluding intensive chemotherapy.

This agent is associated with drug intolerance because of muscle spasms, dysgeusia, and alopecia, however.

The drug is currently in phase 1/2 at a dose of 50 mg orally per day in 20 patients.
 

ROCK2 inhibition

Belumosudil (formerly KD025) “appears to rebalance the immune system,” Dr. Lee said. Investigators think that the drug dampens an autoaggressive inflammatory response by selective inhibition of ROCK2.

This drug has been studied in a dose-escalation study and a phase 2 trial, in which 132 participants were randomized to receive belumosudil 200 mg either once or twice daily.

At a median follow-up of 8 months, the ORR with belumosudil 200 mg once and twice daily was 73% and 74%, respectively. Similar results were seen in patients who had previously received either ruxolitinib or ibrutinib. High response rates were seen in patients with severe chronic GVHD, involvement of four or more organs and a refractory response to their last line of therapy.
 

Hard-to-manage patients

“We’re very hopeful for many of these agents, but we have to acknowledge that there are still many management dilemmas, patients that we just don’t really know what to do with,” Dr. Lee said. “These include patients who have bad sclerosis and fasciitis, nonhealing skin ulcers, bronchiolitis obliterans, serositis that can be very difficult to manage, severe keratoconjunctivitis that can be eyesight threatening, nonhealing mouth ulcers, esophageal structures, and always patients who have frequent infections.

“We are hopeful that some these agents will be useful for our patients who have severe manifestations, but often the number of patients with these manifestations in the trials is too low to say something specific about them,” she added.
 

‘Exciting time’

“It’s an exciting time because there are a lot of different drugs that are being studied for chronic GVHD,” commented Betty Hamilton, MD, a hematologist/oncologist at the Cleveland Clinic.

“I think that where the field is going in terms of treatment is recognizing that chronic GVHD is a pretty heterogeneous disease, and we have to learn even more about the underlying biologic pathways to be able to determine which class of drugs to use and when,” she said in an interview.

She agreed with Dr. Lee that the goals of treating patients with chronic GVHD include improving symptoms and quality, preventing progression, ideally tapering patients off immunosuppression, and achieving a balance between preventing negative consequences of GVHD while maintain the benefits of a graft-versus-leukemia effect.

“In our center, drug choice is based on physician preference and comfort with how often they’ve used the drug, patients’ comorbidities, toxicities of the drug, and logistical considerations,” Dr. Hamilton said.

Dr. Lee disclosed consulting activities for Pfizer and Kadmon, travel and lodging from Amgen, and research funding from those companies and others. Dr. Hamilton disclosed consulting for Syndax and Incyte.

Despite improvements in prevention of graft-versus-host disease, chronic GVHD still occurs in 10%-50% of patients who undergo an allogeneic hematopoietic stem cell transplant, and these patients may require prolonged treatment with multiple lines of therapy, said a hematologist and transplant researcher.

“More effective, less toxic therapies for chronic GVHD are needed,” Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Research Center in Seattle said at the Transplant & Cellular Therapies Meetings.

Dr. Lee reviewed clinical trials for chronic GVHD at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Although the incidence of chronic GVHD has gradually declined over the last 40 years and both relapse-free and overall survival following a chronic GVHD diagnosis have improved, “for patients who are diagnosed with chronic GVHD, they still will see many lines of therapy and many years of therapy,” she said.

Among 148 patients with chronic GVHD treated at her center, for example, 66% went on to two lines of therapy, 50% went on to three lines, 37% required four lines of therapy, and 20% needed five lines or more.

Salvage therapies for patients with chronic GVHD have evolved away from immunomodulators and immunosuppressants in the early 1990s, toward monoclonal antibodies such as rituximab in the early 2000s, to interleukin-2 and to tyrosine kinase inhibitors such as ruxolitinib (Jakafi) and ibrutinib (Imbruvica).

There are currently 36 agents that are FDA approved for at least one indication and can also be prescribed for the treatment of chronic GVHD, Dr. Lee noted.
 

Treatment goals

Dr. Lee laid out six goals for treating patients with chronic GVHD. They include:

• Controlling current signs and symptoms, measured by response rates and patient-reported outcomes
• Preventing further tissue and organ damage
• Minimizing toxicity
• Maintaining graft-versus-tumor effect
• Achieving graft tolerance and stopping immunosuppression
• Decreasing nonrelapse mortality and improving survival

Active trials

Dr. Lee identified 33 trials with chronic GVHD as an indication that are currently recruiting, and an additional 13 trials that are active but closed to recruiting. The trials can be generally grouped by mechanism of action, and involve agents targeting T-regulatory cells, B cells and/or B-cell receptor (BCR) signaling, monocytes/macrophages, costimulatory blockage, a proteasome inhibition, Janus kinase (JAK) 1/2 inhibitors, ROCK2 inhibitors, hedgehog pathway inhibition, cellular therapy, and organ-targeted therapy.

Most of the trials have overall response rate as the primary endpoint, and all but five are currently in phase 1 or 2. The currently active phase 3 trials include two with ibrutinib, one with the investigational agent itacitinib, one with ruxolitinib, and one with mesenchymal stem cells.

“I’ll note that, when results are reported, the denominator really matters for the overall response rate, especially if you’re talking about small trials, because if you require the patient to be treated with an agent for a certain period of time, and you take out all the people who didn’t make it to that time point, then your overall response rate looks better,” she said.
 

BTK inhibitors

The first-in-class Bruton tyrosine kinase (BTK) inhibitor ibrutinib was the first and thus far only agent approved by the Food and Drug Administration for chronic GVHD. The approval was based on a single-arm, multicenter trial with 42 patients.

The ORR in this trial was 69%, consisting of 31% complete responses and 38% partial responses, with a duration of response longer than 10 months in slightly more than half of all patients. In all, 24% of patients had improvement of symptoms in two consecutive visits, and 29% continued on ibrutinib at the time of the primary analysis in 2017.

Based on these promising results, acalabrutinib, which is more potent and selective for BTK than ibrutinib, with no effect on either platelets or natural killer cells, is currently under investigation in a phase 2 trial in 50 patients at a dose of 100 mg orally twice daily.
 

JAK1/2 inhibition

The JAK1 inhibitor itacitinib failed to meet its primary ORR endpoint in the phase 3 GRAVITAS-301 study, according to a press release, but the manufacturer (Incyte) said that it is continuing its commitment to JAK inhibitors with ruxolitinib, which has shown activity against acute, steroid-refractory GVHD, and is being explored for prevention of chronic GVHD in the randomized, phase 3 REACH3 study.

The trial met its primary endpoint for a higher ORR at week 24 with ruxolitinib versus best available therapy, at 49.7% versus 25.6%, respectively, which translated into an odds ratio for response with the JAK inhibitor of 2.99 (P < .0001).
 

Selective T-cell expansion

Efavaleukin alfa is an IL-2-mutated protein (mutein), with a mutation in the IL-2RB-binding portion of IL-2 causing increased selectivity for regulatory T-cell expansion. It is bound to an IgG-Fc domain that is itself mutated, with reduced Fc receptor binding and IgG effector function to give it a longer half life. This agent is being studied in a phase 1/2 trial in a subcutaneous formulation delivered every 1 or 2 weeks to 68 patients.

Monocyte/macrophage depletion

Axatilimab is a high-affinity antibody targeting colony stimulating factor–1 receptor (CSF-1R) expressed on monocytes and macrophages. By blocking CSF-1R, it depletes circulation of nonclassical monocytes and prevents the differentiation and survival of M2 macrophages in tissue.

It is currently being investigated 30 patients in a phase 1/2 study in an intravenous formulation delivered over 30 minutes every 2-4 weeks.
 

Hedgehog pathway inhibition

There is evidence suggesting that hedgehog pathway inhibition can lessen fibrosis. Glasdegib (Daurismo) a potent selective oral inhibitor of the hedgehog signaling pathway, is approved for use with low-dose cytarabine for patients with newly diagnosed acute myeloid leukemia aged older than 75 years or have comorbidities precluding intensive chemotherapy.

This agent is associated with drug intolerance because of muscle spasms, dysgeusia, and alopecia, however.

The drug is currently in phase 1/2 at a dose of 50 mg orally per day in 20 patients.
 

ROCK2 inhibition

Belumosudil (formerly KD025) “appears to rebalance the immune system,” Dr. Lee said. Investigators think that the drug dampens an autoaggressive inflammatory response by selective inhibition of ROCK2.

This drug has been studied in a dose-escalation study and a phase 2 trial, in which 132 participants were randomized to receive belumosudil 200 mg either once or twice daily.

At a median follow-up of 8 months, the ORR with belumosudil 200 mg once and twice daily was 73% and 74%, respectively. Similar results were seen in patients who had previously received either ruxolitinib or ibrutinib. High response rates were seen in patients with severe chronic GVHD, involvement of four or more organs and a refractory response to their last line of therapy.
 

Hard-to-manage patients

“We’re very hopeful for many of these agents, but we have to acknowledge that there are still many management dilemmas, patients that we just don’t really know what to do with,” Dr. Lee said. “These include patients who have bad sclerosis and fasciitis, nonhealing skin ulcers, bronchiolitis obliterans, serositis that can be very difficult to manage, severe keratoconjunctivitis that can be eyesight threatening, nonhealing mouth ulcers, esophageal structures, and always patients who have frequent infections.

“We are hopeful that some these agents will be useful for our patients who have severe manifestations, but often the number of patients with these manifestations in the trials is too low to say something specific about them,” she added.
 

‘Exciting time’

“It’s an exciting time because there are a lot of different drugs that are being studied for chronic GVHD,” commented Betty Hamilton, MD, a hematologist/oncologist at the Cleveland Clinic.

“I think that where the field is going in terms of treatment is recognizing that chronic GVHD is a pretty heterogeneous disease, and we have to learn even more about the underlying biologic pathways to be able to determine which class of drugs to use and when,” she said in an interview.

She agreed with Dr. Lee that the goals of treating patients with chronic GVHD include improving symptoms and quality, preventing progression, ideally tapering patients off immunosuppression, and achieving a balance between preventing negative consequences of GVHD while maintain the benefits of a graft-versus-leukemia effect.

“In our center, drug choice is based on physician preference and comfort with how often they’ve used the drug, patients’ comorbidities, toxicities of the drug, and logistical considerations,” Dr. Hamilton said.

Dr. Lee disclosed consulting activities for Pfizer and Kadmon, travel and lodging from Amgen, and research funding from those companies and others. Dr. Hamilton disclosed consulting for Syndax and Incyte.

Despite improvements in prevention of graft-versus-host disease, chronic GVHD still occurs in 10%-50% of patients who undergo an allogeneic hematopoietic stem cell transplant, and these patients may require prolonged treatment with multiple lines of therapy, said a hematologist and transplant researcher.

“More effective, less toxic therapies for chronic GVHD are needed,” Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Research Center in Seattle said at the Transplant & Cellular Therapies Meetings.

Dr. Lee reviewed clinical trials for chronic GVHD at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Although the incidence of chronic GVHD has gradually declined over the last 40 years and both relapse-free and overall survival following a chronic GVHD diagnosis have improved, “for patients who are diagnosed with chronic GVHD, they still will see many lines of therapy and many years of therapy,” she said.

Among 148 patients with chronic GVHD treated at her center, for example, 66% went on to two lines of therapy, 50% went on to three lines, 37% required four lines of therapy, and 20% needed five lines or more.

Salvage therapies for patients with chronic GVHD have evolved away from immunomodulators and immunosuppressants in the early 1990s, toward monoclonal antibodies such as rituximab in the early 2000s, to interleukin-2 and to tyrosine kinase inhibitors such as ruxolitinib (Jakafi) and ibrutinib (Imbruvica).

There are currently 36 agents that are FDA approved for at least one indication and can also be prescribed for the treatment of chronic GVHD, Dr. Lee noted.
 

Treatment goals

Dr. Lee laid out six goals for treating patients with chronic GVHD. They include:

• Controlling current signs and symptoms, measured by response rates and patient-reported outcomes
• Preventing further tissue and organ damage
• Minimizing toxicity
• Maintaining graft-versus-tumor effect
• Achieving graft tolerance and stopping immunosuppression
• Decreasing nonrelapse mortality and improving survival

Active trials

Dr. Lee identified 33 trials with chronic GVHD as an indication that are currently recruiting, and an additional 13 trials that are active but closed to recruiting. The trials can be generally grouped by mechanism of action, and involve agents targeting T-regulatory cells, B cells and/or B-cell receptor (BCR) signaling, monocytes/macrophages, costimulatory blockage, a proteasome inhibition, Janus kinase (JAK) 1/2 inhibitors, ROCK2 inhibitors, hedgehog pathway inhibition, cellular therapy, and organ-targeted therapy.

Most of the trials have overall response rate as the primary endpoint, and all but five are currently in phase 1 or 2. The currently active phase 3 trials include two with ibrutinib, one with the investigational agent itacitinib, one with ruxolitinib, and one with mesenchymal stem cells.

“I’ll note that, when results are reported, the denominator really matters for the overall response rate, especially if you’re talking about small trials, because if you require the patient to be treated with an agent for a certain period of time, and you take out all the people who didn’t make it to that time point, then your overall response rate looks better,” she said.
 

BTK inhibitors

The first-in-class Bruton tyrosine kinase (BTK) inhibitor ibrutinib was the first and thus far only agent approved by the Food and Drug Administration for chronic GVHD. The approval was based on a single-arm, multicenter trial with 42 patients.

The ORR in this trial was 69%, consisting of 31% complete responses and 38% partial responses, with a duration of response longer than 10 months in slightly more than half of all patients. In all, 24% of patients had improvement of symptoms in two consecutive visits, and 29% continued on ibrutinib at the time of the primary analysis in 2017.

Based on these promising results, acalabrutinib, which is more potent and selective for BTK than ibrutinib, with no effect on either platelets or natural killer cells, is currently under investigation in a phase 2 trial in 50 patients at a dose of 100 mg orally twice daily.
 

JAK1/2 inhibition

The JAK1 inhibitor itacitinib failed to meet its primary ORR endpoint in the phase 3 GRAVITAS-301 study, according to a press release, but the manufacturer (Incyte) said that it is continuing its commitment to JAK inhibitors with ruxolitinib, which has shown activity against acute, steroid-refractory GVHD, and is being explored for prevention of chronic GVHD in the randomized, phase 3 REACH3 study.

The trial met its primary endpoint for a higher ORR at week 24 with ruxolitinib versus best available therapy, at 49.7% versus 25.6%, respectively, which translated into an odds ratio for response with the JAK inhibitor of 2.99 (P < .0001).
 

Selective T-cell expansion

Efavaleukin alfa is an IL-2-mutated protein (mutein), with a mutation in the IL-2RB-binding portion of IL-2 causing increased selectivity for regulatory T-cell expansion. It is bound to an IgG-Fc domain that is itself mutated, with reduced Fc receptor binding and IgG effector function to give it a longer half life. This agent is being studied in a phase 1/2 trial in a subcutaneous formulation delivered every 1 or 2 weeks to 68 patients.

Monocyte/macrophage depletion

Axatilimab is a high-affinity antibody targeting colony stimulating factor–1 receptor (CSF-1R) expressed on monocytes and macrophages. By blocking CSF-1R, it depletes circulation of nonclassical monocytes and prevents the differentiation and survival of M2 macrophages in tissue.

It is currently being investigated 30 patients in a phase 1/2 study in an intravenous formulation delivered over 30 minutes every 2-4 weeks.
 

Hedgehog pathway inhibition

There is evidence suggesting that hedgehog pathway inhibition can lessen fibrosis. Glasdegib (Daurismo) a potent selective oral inhibitor of the hedgehog signaling pathway, is approved for use with low-dose cytarabine for patients with newly diagnosed acute myeloid leukemia aged older than 75 years or have comorbidities precluding intensive chemotherapy.

This agent is associated with drug intolerance because of muscle spasms, dysgeusia, and alopecia, however.

The drug is currently in phase 1/2 at a dose of 50 mg orally per day in 20 patients.
 

ROCK2 inhibition

Belumosudil (formerly KD025) “appears to rebalance the immune system,” Dr. Lee said. Investigators think that the drug dampens an autoaggressive inflammatory response by selective inhibition of ROCK2.

This drug has been studied in a dose-escalation study and a phase 2 trial, in which 132 participants were randomized to receive belumosudil 200 mg either once or twice daily.

At a median follow-up of 8 months, the ORR with belumosudil 200 mg once and twice daily was 73% and 74%, respectively. Similar results were seen in patients who had previously received either ruxolitinib or ibrutinib. High response rates were seen in patients with severe chronic GVHD, involvement of four or more organs and a refractory response to their last line of therapy.
 

Hard-to-manage patients

“We’re very hopeful for many of these agents, but we have to acknowledge that there are still many management dilemmas, patients that we just don’t really know what to do with,” Dr. Lee said. “These include patients who have bad sclerosis and fasciitis, nonhealing skin ulcers, bronchiolitis obliterans, serositis that can be very difficult to manage, severe keratoconjunctivitis that can be eyesight threatening, nonhealing mouth ulcers, esophageal structures, and always patients who have frequent infections.

“We are hopeful that some these agents will be useful for our patients who have severe manifestations, but often the number of patients with these manifestations in the trials is too low to say something specific about them,” she added.
 

‘Exciting time’

“It’s an exciting time because there are a lot of different drugs that are being studied for chronic GVHD,” commented Betty Hamilton, MD, a hematologist/oncologist at the Cleveland Clinic.

“I think that where the field is going in terms of treatment is recognizing that chronic GVHD is a pretty heterogeneous disease, and we have to learn even more about the underlying biologic pathways to be able to determine which class of drugs to use and when,” she said in an interview.

She agreed with Dr. Lee that the goals of treating patients with chronic GVHD include improving symptoms and quality, preventing progression, ideally tapering patients off immunosuppression, and achieving a balance between preventing negative consequences of GVHD while maintain the benefits of a graft-versus-leukemia effect.

“In our center, drug choice is based on physician preference and comfort with how often they’ve used the drug, patients’ comorbidities, toxicities of the drug, and logistical considerations,” Dr. Hamilton said.

Dr. Lee disclosed consulting activities for Pfizer and Kadmon, travel and lodging from Amgen, and research funding from those companies and others. Dr. Hamilton disclosed consulting for Syndax and Incyte.

All patients receiving active cancer treatment should receive a COVID-19 vaccine and should be prioritized for vaccination, according to preliminary recommendations from the National Comprehensive Cancer Network (NCCN).

Vaccination timing considerations vary based on factors such as cancer and treatment type, and reasons for delaying vaccination in the general public also apply to cancer patients (recent COVID-19 exposure, for example).

In general, however, patients with cancer should be assigned to Centers for Disease Control and Prevention priority group 1 b/c and immunized when vaccination is available to them, the guidelines state. Exceptions to this recommendation include:

• Patients undergoing hematopoietic stem cell transplant or receiving engineered cellular therapy such as chimeric antigen receptor T-cell therapy. Vaccination should be delayed for at least 3 months in these patients to maximize vaccine efficacy. Caregivers of these patients, however, should be immunized when possible.
• Patients with hematologic malignancies who are receiving intensive cytotoxic chemotherapy, such as cytarabine- or anthracycline-based regimens for acute myeloid leukemia. Vaccination in these patients should be delayed until absolute neutrophil count recovery.
• Patients undergoing major surgery. Vaccination should occur at least a few days before or after surgery.
• Patients who have experienced a severe or immediate adverse reaction to any of the ingredients in the mRNA COVID-19 vaccines.

Conversely, vaccination should occur when available in patients with hematologic malignancies and marrow failure who are expected to have limited or no recovery, patients with hematologic malignancies who are on long-term maintenance therapy, and patients with solid tumors who are receiving cytotoxic chemotherapy, targeted therapy, checkpoint inhibitors and other immunotherapy, or radiotherapy.

Caregivers, household contacts, and other close contacts who are 16 years of age and older should be vaccinated whenever they are eligible.
 

Unique concerns in patients with cancer

The NCCN recommendations were developed to address the unique issues and concerns with respect to patients with cancer, who have an increased risk of severe illness from SARS-CoV-2 infection. But the guidelines come with a caveat: “[t]here are limited safety and efficacy data in these patients,” the NCCN emphasized in a press statement.

“Right now, there is urgent need and limited data,” Steven Pergam, MD, co-leader of the NCCN COVID-19 Vaccination Committee, said in the statement.

“Our number one goal is helping to get the vaccine to as many people as we can,” Dr. Pergam said. “That means following existing national and regional directions for prioritizing people who are more likely to face death or severe illness from COVID-19.”

Dr. Pergam, associate professor at Fred Hutchinson Cancer Research Center in Seattle, further explained that “people receiving active cancer treatment are at greater risk for worse outcomes from COVID-19, particularly if they are older and have additional comorbidities, like immunosuppression.”

NCCN’s recommendations couldn’t have come at a better time for patients with cancer, according to Nora Disis, MD, a professor at the University of Washington in Seattle.

“The NCCN’s recommendations to prioritize COVID vaccinations for cancer patients on active treatment is an important step forward in protecting our patients from the infection,” Dr. Disis said in an interview.

“Cancer patients may be at higher risk for the complications seen with infection. In addition, cancer is a disease of older people, and a good number of our patients have the comorbidities that would predict a poorer outcome if they should become sick,” Dr. Disis added. “With the correct treatment, many patients with cancer will be long-term survivors. It is important that they be protected from infection with COVID to realize their best outcome.”
 

Additional vaccine considerations

The NCCN recommendations also address several other issues of importance for cancer patients, including:

• Deprioritizing other vaccines. COVID-19 vaccines should take precedence over other vaccines because data on dual vaccination are lacking. The NCCN recommends waiting 14 days after COVID-19 vaccination to deliver other vaccines.
• Vaccinating clinical trial participants. Trial leads should be consulted to prevent protocol violations or exclusions.
• Decision-making in the setting of limited vaccine availability. The NCCN noted that decisions on allocation must be made in accordance with state and local vaccine guidance but suggests prioritizing appropriate patients on active treatment, those planning to start treatment, and those who have just completed treatment. Additional risk factors for these patients, as well as other factors associated with risk for adverse COVID-19 outcomes, should also be considered. These include advanced age, comorbidities, and adverse social and demographic factors such as poverty and limited health care access.
• The need for ongoing prevention measures. Vaccines have been shown to decrease the incidence of COVID-19 and related complications, but it remains unclear whether vaccines prevent infection and subsequent transmission. This means everyone should continue following prevention recommendations, such as wearing masks and avoiding crowds.

The NCCN stressed that these recommendations are “intended to be a living document that is constantly evolving – it will be updated rapidly whenever new data comes out, as well as any potential new vaccines that may get approved in the future.” The NCCN also noted that the advisory committee will meet regularly to refine the recommendations as needed.

Dr. Pergam disclosed relationships with Chimerix Inc., Merck & Co., Global Life Technologies Inc., and Sanofi-Aventis. Dr. Disis disclosed grants from Pfizer, Bavarian Nordisk, Janssen, and Precigen. She is the founder of EpiThany and editor-in-chief of JAMA Oncology.

sworcester@mdedge.com

All patients receiving active cancer treatment should receive a COVID-19 vaccine and should be prioritized for vaccination, according to preliminary recommendations from the National Comprehensive Cancer Network (NCCN).

Vaccination timing considerations vary based on factors such as cancer and treatment type, and reasons for delaying vaccination in the general public also apply to cancer patients (recent COVID-19 exposure, for example).

In general, however, patients with cancer should be assigned to Centers for Disease Control and Prevention priority group 1 b/c and immunized when vaccination is available to them, the guidelines state. Exceptions to this recommendation include:

• Patients undergoing hematopoietic stem cell transplant or receiving engineered cellular therapy such as chimeric antigen receptor T-cell therapy. Vaccination should be delayed for at least 3 months in these patients to maximize vaccine efficacy. Caregivers of these patients, however, should be immunized when possible.
• Patients with hematologic malignancies who are receiving intensive cytotoxic chemotherapy, such as cytarabine- or anthracycline-based regimens for acute myeloid leukemia. Vaccination in these patients should be delayed until absolute neutrophil count recovery.
• Patients undergoing major surgery. Vaccination should occur at least a few days before or after surgery.
• Patients who have experienced a severe or immediate adverse reaction to any of the ingredients in the mRNA COVID-19 vaccines.

Conversely, vaccination should occur when available in patients with hematologic malignancies and marrow failure who are expected to have limited or no recovery, patients with hematologic malignancies who are on long-term maintenance therapy, and patients with solid tumors who are receiving cytotoxic chemotherapy, targeted therapy, checkpoint inhibitors and other immunotherapy, or radiotherapy.

Caregivers, household contacts, and other close contacts who are 16 years of age and older should be vaccinated whenever they are eligible.
 

Unique concerns in patients with cancer

The NCCN recommendations were developed to address the unique issues and concerns with respect to patients with cancer, who have an increased risk of severe illness from SARS-CoV-2 infection. But the guidelines come with a caveat: “[t]here are limited safety and efficacy data in these patients,” the NCCN emphasized in a press statement.

“Right now, there is urgent need and limited data,” Steven Pergam, MD, co-leader of the NCCN COVID-19 Vaccination Committee, said in the statement.

“Our number one goal is helping to get the vaccine to as many people as we can,” Dr. Pergam said. “That means following existing national and regional directions for prioritizing people who are more likely to face death or severe illness from COVID-19.”

Dr. Pergam, associate professor at Fred Hutchinson Cancer Research Center in Seattle, further explained that “people receiving active cancer treatment are at greater risk for worse outcomes from COVID-19, particularly if they are older and have additional comorbidities, like immunosuppression.”

NCCN’s recommendations couldn’t have come at a better time for patients with cancer, according to Nora Disis, MD, a professor at the University of Washington in Seattle.

“The NCCN’s recommendations to prioritize COVID vaccinations for cancer patients on active treatment is an important step forward in protecting our patients from the infection,” Dr. Disis said in an interview.

“Cancer patients may be at higher risk for the complications seen with infection. In addition, cancer is a disease of older people, and a good number of our patients have the comorbidities that would predict a poorer outcome if they should become sick,” Dr. Disis added. “With the correct treatment, many patients with cancer will be long-term survivors. It is important that they be protected from infection with COVID to realize their best outcome.”
 

Additional vaccine considerations

The NCCN recommendations also address several other issues of importance for cancer patients, including:

• Deprioritizing other vaccines. COVID-19 vaccines should take precedence over other vaccines because data on dual vaccination are lacking. The NCCN recommends waiting 14 days after COVID-19 vaccination to deliver other vaccines.
• Vaccinating clinical trial participants. Trial leads should be consulted to prevent protocol violations or exclusions.
• Decision-making in the setting of limited vaccine availability. The NCCN noted that decisions on allocation must be made in accordance with state and local vaccine guidance but suggests prioritizing appropriate patients on active treatment, those planning to start treatment, and those who have just completed treatment. Additional risk factors for these patients, as well as other factors associated with risk for adverse COVID-19 outcomes, should also be considered. These include advanced age, comorbidities, and adverse social and demographic factors such as poverty and limited health care access.
• The need for ongoing prevention measures. Vaccines have been shown to decrease the incidence of COVID-19 and related complications, but it remains unclear whether vaccines prevent infection and subsequent transmission. This means everyone should continue following prevention recommendations, such as wearing masks and avoiding crowds.

The NCCN stressed that these recommendations are “intended to be a living document that is constantly evolving – it will be updated rapidly whenever new data comes out, as well as any potential new vaccines that may get approved in the future.” The NCCN also noted that the advisory committee will meet regularly to refine the recommendations as needed.

Dr. Pergam disclosed relationships with Chimerix Inc., Merck & Co., Global Life Technologies Inc., and Sanofi-Aventis. Dr. Disis disclosed grants from Pfizer, Bavarian Nordisk, Janssen, and Precigen. She is the founder of EpiThany and editor-in-chief of JAMA Oncology.

sworcester@mdedge.com

All patients receiving active cancer treatment should receive a COVID-19 vaccine and should be prioritized for vaccination, according to preliminary recommendations from the National Comprehensive Cancer Network (NCCN).

Vaccination timing considerations vary based on factors such as cancer and treatment type, and reasons for delaying vaccination in the general public also apply to cancer patients (recent COVID-19 exposure, for example).

In general, however, patients with cancer should be assigned to Centers for Disease Control and Prevention priority group 1 b/c and immunized when vaccination is available to them, the guidelines state. Exceptions to this recommendation include:

• Patients undergoing hematopoietic stem cell transplant or receiving engineered cellular therapy such as chimeric antigen receptor T-cell therapy. Vaccination should be delayed for at least 3 months in these patients to maximize vaccine efficacy. Caregivers of these patients, however, should be immunized when possible.
• Patients with hematologic malignancies who are receiving intensive cytotoxic chemotherapy, such as cytarabine- or anthracycline-based regimens for acute myeloid leukemia. Vaccination in these patients should be delayed until absolute neutrophil count recovery.
• Patients undergoing major surgery. Vaccination should occur at least a few days before or after surgery.
• Patients who have experienced a severe or immediate adverse reaction to any of the ingredients in the mRNA COVID-19 vaccines.

Conversely, vaccination should occur when available in patients with hematologic malignancies and marrow failure who are expected to have limited or no recovery, patients with hematologic malignancies who are on long-term maintenance therapy, and patients with solid tumors who are receiving cytotoxic chemotherapy, targeted therapy, checkpoint inhibitors and other immunotherapy, or radiotherapy.

Caregivers, household contacts, and other close contacts who are 16 years of age and older should be vaccinated whenever they are eligible.
 

Unique concerns in patients with cancer

The NCCN recommendations were developed to address the unique issues and concerns with respect to patients with cancer, who have an increased risk of severe illness from SARS-CoV-2 infection. But the guidelines come with a caveat: “[t]here are limited safety and efficacy data in these patients,” the NCCN emphasized in a press statement.

“Right now, there is urgent need and limited data,” Steven Pergam, MD, co-leader of the NCCN COVID-19 Vaccination Committee, said in the statement.

“Our number one goal is helping to get the vaccine to as many people as we can,” Dr. Pergam said. “That means following existing national and regional directions for prioritizing people who are more likely to face death or severe illness from COVID-19.”

Dr. Pergam, associate professor at Fred Hutchinson Cancer Research Center in Seattle, further explained that “people receiving active cancer treatment are at greater risk for worse outcomes from COVID-19, particularly if they are older and have additional comorbidities, like immunosuppression.”

NCCN’s recommendations couldn’t have come at a better time for patients with cancer, according to Nora Disis, MD, a professor at the University of Washington in Seattle.

“The NCCN’s recommendations to prioritize COVID vaccinations for cancer patients on active treatment is an important step forward in protecting our patients from the infection,” Dr. Disis said in an interview.

“Cancer patients may be at higher risk for the complications seen with infection. In addition, cancer is a disease of older people, and a good number of our patients have the comorbidities that would predict a poorer outcome if they should become sick,” Dr. Disis added. “With the correct treatment, many patients with cancer will be long-term survivors. It is important that they be protected from infection with COVID to realize their best outcome.”
 

Additional vaccine considerations

The NCCN recommendations also address several other issues of importance for cancer patients, including:

• Deprioritizing other vaccines. COVID-19 vaccines should take precedence over other vaccines because data on dual vaccination are lacking. The NCCN recommends waiting 14 days after COVID-19 vaccination to deliver other vaccines.
• Vaccinating clinical trial participants. Trial leads should be consulted to prevent protocol violations or exclusions.
• Decision-making in the setting of limited vaccine availability. The NCCN noted that decisions on allocation must be made in accordance with state and local vaccine guidance but suggests prioritizing appropriate patients on active treatment, those planning to start treatment, and those who have just completed treatment. Additional risk factors for these patients, as well as other factors associated with risk for adverse COVID-19 outcomes, should also be considered. These include advanced age, comorbidities, and adverse social and demographic factors such as poverty and limited health care access.
• The need for ongoing prevention measures. Vaccines have been shown to decrease the incidence of COVID-19 and related complications, but it remains unclear whether vaccines prevent infection and subsequent transmission. This means everyone should continue following prevention recommendations, such as wearing masks and avoiding crowds.

The NCCN stressed that these recommendations are “intended to be a living document that is constantly evolving – it will be updated rapidly whenever new data comes out, as well as any potential new vaccines that may get approved in the future.” The NCCN also noted that the advisory committee will meet regularly to refine the recommendations as needed.

Dr. Pergam disclosed relationships with Chimerix Inc., Merck & Co., Global Life Technologies Inc., and Sanofi-Aventis. Dr. Disis disclosed grants from Pfizer, Bavarian Nordisk, Janssen, and Precigen. She is the founder of EpiThany and editor-in-chief of JAMA Oncology.

sworcester@mdedge.com

Tending to patients who opt for outpatient autologous stem cell transplants is well tolerated by caregivers, so long as they have the resources and support necessary, according to a recent Italian report.

Investigators surveyed the primary caregivers – most often the spouse – of 25 multiple myeloma patients who, in consultation with their caregiver, opted for an outpatient procedure and 71 others who chose standard inpatient treatment, and compared the results. Outpatients were discharged a day after transplant with twice-weekly clinic visits until sustained hematologic recovery as reported in Clinical Lymphoma, Myeloma and Leukemia.

The teams used portions of the Caregiver Reaction Assessment survey that focused on self-reported sense of family support plus affect on daily activities and general health. Surveys were taken a week before transplant and 3 months afterwards.

Results did not differ significantly between outpatient and inpatient caregivers at either point, and there was no meaningful change in responses over time.

“The outpatient model neither improves nor impairs global caregivers’ burden, compared with” inpatient transplant. Outpatient caregivers “do not show that they suffer from a greater burden of responsibility as compared to those belonging to the inpatient’s arm,” said investigators led by Massimo Martino, MD, director of stem cell transplants at the Great Metropolitan Hospital in Reggio Calabria, Italy, where the patients were treated.

The relatively short-lasting neutropenia and the limited nonhematologic toxicity of high-dose melphalan make multiple myeloma good candidates for outpatient programs. Indeed, the incidence rate of mucositis, fever, chemotherapy-induced nausea and vomiting, and other adverse events did not differ between in and outpatients, which is in keeping with previous reports supporting the feasibility and safety of outpatient programs.

However, the burden on loved ones is considerable. At least during the aplastic phase, outpatient caregivers are on call around the clock and spend most of their time with the patient. Homes have to be kept meticulously clean, vital signs checked, medications administered, and ins and outs monitored, among other duties normally handled by inpatient staff.

The main limit of the study was that outpatients were a self-selected group. They and their caregivers may simply have had the resources and support needed for successful outpatient transplants, while other patients did not. As the investigators put it, “we cannot exclude the problem of residual confounding due to unmeasured variables” such as “factors underlying patients’ preference, which could potentially impact the study results.”

Administering the follow-up survey 3 months after transplant might also have missed the acute impact on outpatient caregivers. It’s been “reported that the quality of life of patients undergoing an” outpatient procedure decreases immediately post treatment but bounces back by 6 months. “The same result can probably be observed in caregivers,” the team said.

The outpatient and inpatient groups were comparable, with a majority of men and a mean age of about 60 years in both. The number of infused stem cells, engraftment kinetics, and hematopoietic cell transplantation–comorbidity index scores did not differ significantly between the two groups.

There was no funding for the work, and the investigators reported that they didn’t have any conflicts of interest.

aotto@mdedge.com

SOURCE: Martino M et al. Clin Lymphoma Myeloma Leuk. 2020 Nov 19. doi: 10.1016/j.clml.2020.11.011.

Tending to patients who opt for outpatient autologous stem cell transplants is well tolerated by caregivers, so long as they have the resources and support necessary, according to a recent Italian report.

Investigators surveyed the primary caregivers – most often the spouse – of 25 multiple myeloma patients who, in consultation with their caregiver, opted for an outpatient procedure and 71 others who chose standard inpatient treatment, and compared the results. Outpatients were discharged a day after transplant with twice-weekly clinic visits until sustained hematologic recovery as reported in Clinical Lymphoma, Myeloma and Leukemia.

The teams used portions of the Caregiver Reaction Assessment survey that focused on self-reported sense of family support plus affect on daily activities and general health. Surveys were taken a week before transplant and 3 months afterwards.

Results did not differ significantly between outpatient and inpatient caregivers at either point, and there was no meaningful change in responses over time.

“The outpatient model neither improves nor impairs global caregivers’ burden, compared with” inpatient transplant. Outpatient caregivers “do not show that they suffer from a greater burden of responsibility as compared to those belonging to the inpatient’s arm,” said investigators led by Massimo Martino, MD, director of stem cell transplants at the Great Metropolitan Hospital in Reggio Calabria, Italy, where the patients were treated.

The relatively short-lasting neutropenia and the limited nonhematologic toxicity of high-dose melphalan make multiple myeloma good candidates for outpatient programs. Indeed, the incidence rate of mucositis, fever, chemotherapy-induced nausea and vomiting, and other adverse events did not differ between in and outpatients, which is in keeping with previous reports supporting the feasibility and safety of outpatient programs.

However, the burden on loved ones is considerable. At least during the aplastic phase, outpatient caregivers are on call around the clock and spend most of their time with the patient. Homes have to be kept meticulously clean, vital signs checked, medications administered, and ins and outs monitored, among other duties normally handled by inpatient staff.

The main limit of the study was that outpatients were a self-selected group. They and their caregivers may simply have had the resources and support needed for successful outpatient transplants, while other patients did not. As the investigators put it, “we cannot exclude the problem of residual confounding due to unmeasured variables” such as “factors underlying patients’ preference, which could potentially impact the study results.”

Administering the follow-up survey 3 months after transplant might also have missed the acute impact on outpatient caregivers. It’s been “reported that the quality of life of patients undergoing an” outpatient procedure decreases immediately post treatment but bounces back by 6 months. “The same result can probably be observed in caregivers,” the team said.

The outpatient and inpatient groups were comparable, with a majority of men and a mean age of about 60 years in both. The number of infused stem cells, engraftment kinetics, and hematopoietic cell transplantation–comorbidity index scores did not differ significantly between the two groups.

There was no funding for the work, and the investigators reported that they didn’t have any conflicts of interest.

aotto@mdedge.com

SOURCE: Martino M et al. Clin Lymphoma Myeloma Leuk. 2020 Nov 19. doi: 10.1016/j.clml.2020.11.011.

Tending to patients who opt for outpatient autologous stem cell transplants is well tolerated by caregivers, so long as they have the resources and support necessary, according to a recent Italian report.

Investigators surveyed the primary caregivers – most often the spouse – of 25 multiple myeloma patients who, in consultation with their caregiver, opted for an outpatient procedure and 71 others who chose standard inpatient treatment, and compared the results. Outpatients were discharged a day after transplant with twice-weekly clinic visits until sustained hematologic recovery as reported in Clinical Lymphoma, Myeloma and Leukemia.

The teams used portions of the Caregiver Reaction Assessment survey that focused on self-reported sense of family support plus affect on daily activities and general health. Surveys were taken a week before transplant and 3 months afterwards.

Results did not differ significantly between outpatient and inpatient caregivers at either point, and there was no meaningful change in responses over time.

“The outpatient model neither improves nor impairs global caregivers’ burden, compared with” inpatient transplant. Outpatient caregivers “do not show that they suffer from a greater burden of responsibility as compared to those belonging to the inpatient’s arm,” said investigators led by Massimo Martino, MD, director of stem cell transplants at the Great Metropolitan Hospital in Reggio Calabria, Italy, where the patients were treated.

The relatively short-lasting neutropenia and the limited nonhematologic toxicity of high-dose melphalan make multiple myeloma good candidates for outpatient programs. Indeed, the incidence rate of mucositis, fever, chemotherapy-induced nausea and vomiting, and other adverse events did not differ between in and outpatients, which is in keeping with previous reports supporting the feasibility and safety of outpatient programs.

However, the burden on loved ones is considerable. At least during the aplastic phase, outpatient caregivers are on call around the clock and spend most of their time with the patient. Homes have to be kept meticulously clean, vital signs checked, medications administered, and ins and outs monitored, among other duties normally handled by inpatient staff.

The main limit of the study was that outpatients were a self-selected group. They and their caregivers may simply have had the resources and support needed for successful outpatient transplants, while other patients did not. As the investigators put it, “we cannot exclude the problem of residual confounding due to unmeasured variables” such as “factors underlying patients’ preference, which could potentially impact the study results.”

Administering the follow-up survey 3 months after transplant might also have missed the acute impact on outpatient caregivers. It’s been “reported that the quality of life of patients undergoing an” outpatient procedure decreases immediately post treatment but bounces back by 6 months. “The same result can probably be observed in caregivers,” the team said.

The outpatient and inpatient groups were comparable, with a majority of men and a mean age of about 60 years in both. The number of infused stem cells, engraftment kinetics, and hematopoietic cell transplantation–comorbidity index scores did not differ significantly between the two groups.

There was no funding for the work, and the investigators reported that they didn’t have any conflicts of interest.

aotto@mdedge.com

SOURCE: Martino M et al. Clin Lymphoma Myeloma Leuk. 2020 Nov 19. doi: 10.1016/j.clml.2020.11.011.

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma. 

The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine. 

Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York. 

“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.

Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.

Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said. 

Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
 

Shedding of viable virus

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).  

Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.

There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection. 

In total, 78 respiratory samples were collected.

“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes and found that  “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.

The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma. 

The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine. 

Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York. 

“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.

Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.

Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said. 

Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
 

Shedding of viable virus

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).  

Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.

There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection. 

In total, 78 respiratory samples were collected.

“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes and found that  “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.

The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma. 

The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine. 

Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York. 

“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.

Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.

Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said. 

Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
 

Shedding of viable virus

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).  

Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.

There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection. 

In total, 78 respiratory samples were collected.

“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes and found that  “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.

The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

When chronic graft-versus-host disease (cGVHD) develops as a complication of allogeneic hematopoietic stem cell transplant (alloHSCT), treatment options are limited. New findings show that ruxolitinib (Jakafi) was superior to standard therapy in reducing symptoms of cGVHD in the second-line setting, and the results are potentially practice changing.  

The new data, from the REACH3 trial, were presented at the annual meeting of the American Society of Hematology, held virtually this year.

This trial is “almost certainly a practice changer,” Robert Brodsky, MD, ASH secretary, said during a press preview webinar.  

Chronic GVHD occurs in approximately 30%-70% of patients who undergo alloSCT, and “has been really hard to treat,” said Dr. Brodsky, of Johns Hopkins University, Baltimore. “Steroids are the first-line treatment, but after that, nothing else has shown any improvement and even steroids don’t work that well.”

Of the patients assessed, 50% of those who received ruxolitinib responded to therapy compared with only 25% who received standard therapies.

“This is the first multicenter randomized controlled trial for chronic GVHD that is positive,” said senior study author Robert Zeiser, PhD, of University Medical Center, Freiburg, Germany. “It shows a significant advantage for ruxolitinib. It is likely that this trial will lead to approval for this indication and change the guidelines for the treatment of this disease.”

Ruxolitinib, a JAK inhibitor first marketed for use in myelofibrosis, is already  approved for acute GVHD. The Food and Drug Administration approved that indication last year on the basis of data from two previous trials, REACH 1 and REACH 2. The trials found that ruxolitinib was superior to best available therapy for treating patients with acute GVHD.
 

Superior to best available therapy

In the current REACH 3 study, Dr. Zeiser and colleagues compared ruxolitinib with best available therapy in 329 patients with moderate-to-severe cGVHD (both steroid dependent and steroid resistant).

All patients had undergone alloSCT and were randomly assigned to ruxolitinib (10 mg twice daily) for six 28-day cycles or investigator-selected best available therapy (BAT), of which there were 10 options. Patients continued receiving their regimen of corticosteroids, and viral prophylaxis and antibiotics were allowed as needed for infection prevention and treatment.

The study permitted crossover: Patients on BAT were allowed to start on ruxolitinib on or after cycle 7 day 1 for those who did not achieve or maintain a response, developed toxicity to BAT, or had a cGVHD flare.

The study met its primary endpoint of overall response rate (ORR), with a clear and substantial improvement among patients taking ruxolitinib (50% vs 26%; odds ratio, 2.99; P < .0001a), Dr. Zeiser noted. The complete response rate was also higher (7% vs. 3%).

Both key secondary endpoints also showed that ruxolitinib was superior to BAT. Failure-free survival was significantly longer in the ruxolitinib group (median not reached vs 5.7 months; hazard ratio, 0.370; P < .0001). There was also an improvement in symptoms based on changes in the modified Lee symptom score (mLSS; 0 [no symptoms] to 100 [worst symptoms]) at cycle 7 day 1; the results show that the mLSS responder rate was higher in patients on ruxolitinib (24% vs. 11%; odds ratio, 2.62; P = .0011).

A total of 31 patients in the ruxolitinib group died (19%) along with 27 in the BAT group (16%), with the cGVHD as the main cause of death.

Adverse events were comparable in both groups (ruxolitinib 98% [grade ≥ 3, 57%]; BAT, 92% [grade ≥ 3, 58%], with the most common being anemia (29% vs. 13%), hypertension (16% vs. 13%), pyrexia (16% vs. 9%), and ALT increase (15% vs 4%).
 

More options for patients

“The addition of ruxolitinib is definitely practice changing for this very difficult to treat population,” said James Essell, MD,  medical director of the Blood Cancer Center at Mercy Health, Cincinnati, who was not involved in the study.

However, he added, “more options are still required, as evidenced by the continued deaths of patients despite this new option.”

Dr. Essell pointed out that ibrutinib (Imbruvica) is already approved for the treatment of cGVHD. “Ruxolitinib offers another option for treating this group of patients,” he said, and predicted that “it will be used frequently and has a different toxicity profile, ultimately improving the care for patients with cGVHD.”

It is likely that ruxolitinib will be considered earlier in the treatment of cGVHD to avoid the toxicity of chronic steroid use, he added, but price is a consideration. “The cost of ruxolitinib is over 200 times more than prednisone, limiting the adoption front line without a clinical trial.”

Another expert approached for comment was enthusiastic. “The abstract gave good evidence and efficacy with chronic GVHD,” said Ryotaro Nakamura, MD, associate professor of hematology & hematopoietic cell transplantation at City of Hope, Duarte, Calif. He noted that there have been two previous REACH trials which showed a benefit for ruxolitinib in acute GVHD.

What this means is that there is now global evidence that ruxolitinib is better than anything else so far, he said, and this latest trial is just part of the “practice-changing data,” from the three studies. “It is practice changing in that it is providing options now for these patients,” he said.

Dr. Zeiser has disclosed relationships with Incyte, Novartis and Mallinckrodt; other authors disclosed relationships with industry as noted in the abstract. Dr. Essell and Dr. Nakamura have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

When chronic graft-versus-host disease (cGVHD) develops as a complication of allogeneic hematopoietic stem cell transplant (alloHSCT), treatment options are limited. New findings show that ruxolitinib (Jakafi) was superior to standard therapy in reducing symptoms of cGVHD in the second-line setting, and the results are potentially practice changing.  

The new data, from the REACH3 trial, were presented at the annual meeting of the American Society of Hematology, held virtually this year.

This trial is “almost certainly a practice changer,” Robert Brodsky, MD, ASH secretary, said during a press preview webinar.  

Chronic GVHD occurs in approximately 30%-70% of patients who undergo alloSCT, and “has been really hard to treat,” said Dr. Brodsky, of Johns Hopkins University, Baltimore. “Steroids are the first-line treatment, but after that, nothing else has shown any improvement and even steroids don’t work that well.”

Of the patients assessed, 50% of those who received ruxolitinib responded to therapy compared with only 25% who received standard therapies.

“This is the first multicenter randomized controlled trial for chronic GVHD that is positive,” said senior study author Robert Zeiser, PhD, of University Medical Center, Freiburg, Germany. “It shows a significant advantage for ruxolitinib. It is likely that this trial will lead to approval for this indication and change the guidelines for the treatment of this disease.”

Ruxolitinib, a JAK inhibitor first marketed for use in myelofibrosis, is already  approved for acute GVHD. The Food and Drug Administration approved that indication last year on the basis of data from two previous trials, REACH 1 and REACH 2. The trials found that ruxolitinib was superior to best available therapy for treating patients with acute GVHD.
 

Superior to best available therapy

In the current REACH 3 study, Dr. Zeiser and colleagues compared ruxolitinib with best available therapy in 329 patients with moderate-to-severe cGVHD (both steroid dependent and steroid resistant).

All patients had undergone alloSCT and were randomly assigned to ruxolitinib (10 mg twice daily) for six 28-day cycles or investigator-selected best available therapy (BAT), of which there were 10 options. Patients continued receiving their regimen of corticosteroids, and viral prophylaxis and antibiotics were allowed as needed for infection prevention and treatment.

The study permitted crossover: Patients on BAT were allowed to start on ruxolitinib on or after cycle 7 day 1 for those who did not achieve or maintain a response, developed toxicity to BAT, or had a cGVHD flare.

The study met its primary endpoint of overall response rate (ORR), with a clear and substantial improvement among patients taking ruxolitinib (50% vs 26%; odds ratio, 2.99; P < .0001a), Dr. Zeiser noted. The complete response rate was also higher (7% vs. 3%).

Both key secondary endpoints also showed that ruxolitinib was superior to BAT. Failure-free survival was significantly longer in the ruxolitinib group (median not reached vs 5.7 months; hazard ratio, 0.370; P < .0001). There was also an improvement in symptoms based on changes in the modified Lee symptom score (mLSS; 0 [no symptoms] to 100 [worst symptoms]) at cycle 7 day 1; the results show that the mLSS responder rate was higher in patients on ruxolitinib (24% vs. 11%; odds ratio, 2.62; P = .0011).

A total of 31 patients in the ruxolitinib group died (19%) along with 27 in the BAT group (16%), with the cGVHD as the main cause of death.

Adverse events were comparable in both groups (ruxolitinib 98% [grade ≥ 3, 57%]; BAT, 92% [grade ≥ 3, 58%], with the most common being anemia (29% vs. 13%), hypertension (16% vs. 13%), pyrexia (16% vs. 9%), and ALT increase (15% vs 4%).
 

More options for patients

“The addition of ruxolitinib is definitely practice changing for this very difficult to treat population,” said James Essell, MD,  medical director of the Blood Cancer Center at Mercy Health, Cincinnati, who was not involved in the study.

However, he added, “more options are still required, as evidenced by the continued deaths of patients despite this new option.”

Dr. Essell pointed out that ibrutinib (Imbruvica) is already approved for the treatment of cGVHD. “Ruxolitinib offers another option for treating this group of patients,” he said, and predicted that “it will be used frequently and has a different toxicity profile, ultimately improving the care for patients with cGVHD.”

It is likely that ruxolitinib will be considered earlier in the treatment of cGVHD to avoid the toxicity of chronic steroid use, he added, but price is a consideration. “The cost of ruxolitinib is over 200 times more than prednisone, limiting the adoption front line without a clinical trial.”

Another expert approached for comment was enthusiastic. “The abstract gave good evidence and efficacy with chronic GVHD,” said Ryotaro Nakamura, MD, associate professor of hematology & hematopoietic cell transplantation at City of Hope, Duarte, Calif. He noted that there have been two previous REACH trials which showed a benefit for ruxolitinib in acute GVHD.

What this means is that there is now global evidence that ruxolitinib is better than anything else so far, he said, and this latest trial is just part of the “practice-changing data,” from the three studies. “It is practice changing in that it is providing options now for these patients,” he said.

Dr. Zeiser has disclosed relationships with Incyte, Novartis and Mallinckrodt; other authors disclosed relationships with industry as noted in the abstract. Dr. Essell and Dr. Nakamura have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

When chronic graft-versus-host disease (cGVHD) develops as a complication of allogeneic hematopoietic stem cell transplant (alloHSCT), treatment options are limited. New findings show that ruxolitinib (Jakafi) was superior to standard therapy in reducing symptoms of cGVHD in the second-line setting, and the results are potentially practice changing.  

The new data, from the REACH3 trial, were presented at the annual meeting of the American Society of Hematology, held virtually this year.

This trial is “almost certainly a practice changer,” Robert Brodsky, MD, ASH secretary, said during a press preview webinar.  

Chronic GVHD occurs in approximately 30%-70% of patients who undergo alloSCT, and “has been really hard to treat,” said Dr. Brodsky, of Johns Hopkins University, Baltimore. “Steroids are the first-line treatment, but after that, nothing else has shown any improvement and even steroids don’t work that well.”

Of the patients assessed, 50% of those who received ruxolitinib responded to therapy compared with only 25% who received standard therapies.

“This is the first multicenter randomized controlled trial for chronic GVHD that is positive,” said senior study author Robert Zeiser, PhD, of University Medical Center, Freiburg, Germany. “It shows a significant advantage for ruxolitinib. It is likely that this trial will lead to approval for this indication and change the guidelines for the treatment of this disease.”

Ruxolitinib, a JAK inhibitor first marketed for use in myelofibrosis, is already  approved for acute GVHD. The Food and Drug Administration approved that indication last year on the basis of data from two previous trials, REACH 1 and REACH 2. The trials found that ruxolitinib was superior to best available therapy for treating patients with acute GVHD.
 

Superior to best available therapy

In the current REACH 3 study, Dr. Zeiser and colleagues compared ruxolitinib with best available therapy in 329 patients with moderate-to-severe cGVHD (both steroid dependent and steroid resistant).

All patients had undergone alloSCT and were randomly assigned to ruxolitinib (10 mg twice daily) for six 28-day cycles or investigator-selected best available therapy (BAT), of which there were 10 options. Patients continued receiving their regimen of corticosteroids, and viral prophylaxis and antibiotics were allowed as needed for infection prevention and treatment.

The study permitted crossover: Patients on BAT were allowed to start on ruxolitinib on or after cycle 7 day 1 for those who did not achieve or maintain a response, developed toxicity to BAT, or had a cGVHD flare.

The study met its primary endpoint of overall response rate (ORR), with a clear and substantial improvement among patients taking ruxolitinib (50% vs 26%; odds ratio, 2.99; P < .0001a), Dr. Zeiser noted. The complete response rate was also higher (7% vs. 3%).

Both key secondary endpoints also showed that ruxolitinib was superior to BAT. Failure-free survival was significantly longer in the ruxolitinib group (median not reached vs 5.7 months; hazard ratio, 0.370; P < .0001). There was also an improvement in symptoms based on changes in the modified Lee symptom score (mLSS; 0 [no symptoms] to 100 [worst symptoms]) at cycle 7 day 1; the results show that the mLSS responder rate was higher in patients on ruxolitinib (24% vs. 11%; odds ratio, 2.62; P = .0011).

A total of 31 patients in the ruxolitinib group died (19%) along with 27 in the BAT group (16%), with the cGVHD as the main cause of death.

Adverse events were comparable in both groups (ruxolitinib 98% [grade ≥ 3, 57%]; BAT, 92% [grade ≥ 3, 58%], with the most common being anemia (29% vs. 13%), hypertension (16% vs. 13%), pyrexia (16% vs. 9%), and ALT increase (15% vs 4%).
 

More options for patients

“The addition of ruxolitinib is definitely practice changing for this very difficult to treat population,” said James Essell, MD,  medical director of the Blood Cancer Center at Mercy Health, Cincinnati, who was not involved in the study.

However, he added, “more options are still required, as evidenced by the continued deaths of patients despite this new option.”

Dr. Essell pointed out that ibrutinib (Imbruvica) is already approved for the treatment of cGVHD. “Ruxolitinib offers another option for treating this group of patients,” he said, and predicted that “it will be used frequently and has a different toxicity profile, ultimately improving the care for patients with cGVHD.”

It is likely that ruxolitinib will be considered earlier in the treatment of cGVHD to avoid the toxicity of chronic steroid use, he added, but price is a consideration. “The cost of ruxolitinib is over 200 times more than prednisone, limiting the adoption front line without a clinical trial.”

Another expert approached for comment was enthusiastic. “The abstract gave good evidence and efficacy with chronic GVHD,” said Ryotaro Nakamura, MD, associate professor of hematology & hematopoietic cell transplantation at City of Hope, Duarte, Calif. He noted that there have been two previous REACH trials which showed a benefit for ruxolitinib in acute GVHD.

What this means is that there is now global evidence that ruxolitinib is better than anything else so far, he said, and this latest trial is just part of the “practice-changing data,” from the three studies. “It is practice changing in that it is providing options now for these patients,” he said.

Dr. Zeiser has disclosed relationships with Incyte, Novartis and Mallinckrodt; other authors disclosed relationships with industry as noted in the abstract. Dr. Essell and Dr. Nakamura have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Liver transplantation using hepatitis C virus (HCV)-seropositive grafts to HCV-seronegative recipients resulted in “excellent short-term outcomes,” according to the results of a prospective, multicenter study reported in the Journal of Hepatology.

A total of 34 HCV– liver transplantation recipients received grafts from HCV+ donors (20 HCV viremic and 14 nonviremic) from January 2018 to September 2019, according to Bashar Aqel, MD, of the Mayo Clinic, Phoenix, Ariz., and colleagues.

Seven of the grafts were obtained from donation after cardiac death (DCD). Six recipients underwent simultaneous liver/kidney (SLK) transplant, and four patients were repeat liver transplants.
 

Sustained viral response

None of the recipients of an HCV nonviremic graft developed HCV viremia. However, all 20 patients who received HCV viremic grafts had HCV viremia confirmed within 3 days after liver transplant. Direct-acting antiviral (DAA) treatment was started at the median time of 27.5 days in these patients.

All 20 patients successfully completed the treatment and achieved a sustained viral response. In addition, the DAA treatment was well tolerated with minimal adverse events, according to the researchers.

However, one patient died, having developed HCV-related acute membranous nephropathy that resulted in end-stage kidney disease. In addition, a recipient of an HCV nonviremic graft died with acute myocardial infarction 610 days post liver transplant, the authors reported.

“This multicenter study demonstrated LT [liver transplantation] using HCV-seropositive grafts to HCV-seronegative recipients resulted in acceptable short-term outcomes even with the use of DCD grafts and expansion into SLK or repeat LT. However, a careful ongoing assessment regarding patient and graft selection, complications, and the timing of treatment is required,” the researchers concluded.

The study was funded in part by the McIver Estate Young Investigator Benefactor Award. The authors reported they had no potential conflicts.

mlesney@mdedge.com

SOURCE: Aqel B et al. J Hepatol. 2020, Nov 11. doi: 10.1016/j.jhep.2020.11.005.

Liver transplantation using hepatitis C virus (HCV)-seropositive grafts to HCV-seronegative recipients resulted in “excellent short-term outcomes,” according to the results of a prospective, multicenter study reported in the Journal of Hepatology.

A total of 34 HCV– liver transplantation recipients received grafts from HCV+ donors (20 HCV viremic and 14 nonviremic) from January 2018 to September 2019, according to Bashar Aqel, MD, of the Mayo Clinic, Phoenix, Ariz., and colleagues.

Seven of the grafts were obtained from donation after cardiac death (DCD). Six recipients underwent simultaneous liver/kidney (SLK) transplant, and four patients were repeat liver transplants.
 

Sustained viral response

None of the recipients of an HCV nonviremic graft developed HCV viremia. However, all 20 patients who received HCV viremic grafts had HCV viremia confirmed within 3 days after liver transplant. Direct-acting antiviral (DAA) treatment was started at the median time of 27.5 days in these patients.

All 20 patients successfully completed the treatment and achieved a sustained viral response. In addition, the DAA treatment was well tolerated with minimal adverse events, according to the researchers.

However, one patient died, having developed HCV-related acute membranous nephropathy that resulted in end-stage kidney disease. In addition, a recipient of an HCV nonviremic graft died with acute myocardial infarction 610 days post liver transplant, the authors reported.

“This multicenter study demonstrated LT [liver transplantation] using HCV-seropositive grafts to HCV-seronegative recipients resulted in acceptable short-term outcomes even with the use of DCD grafts and expansion into SLK or repeat LT. However, a careful ongoing assessment regarding patient and graft selection, complications, and the timing of treatment is required,” the researchers concluded.

The study was funded in part by the McIver Estate Young Investigator Benefactor Award. The authors reported they had no potential conflicts.

mlesney@mdedge.com

SOURCE: Aqel B et al. J Hepatol. 2020, Nov 11. doi: 10.1016/j.jhep.2020.11.005.

Liver transplantation using hepatitis C virus (HCV)-seropositive grafts to HCV-seronegative recipients resulted in “excellent short-term outcomes,” according to the results of a prospective, multicenter study reported in the Journal of Hepatology.

A total of 34 HCV– liver transplantation recipients received grafts from HCV+ donors (20 HCV viremic and 14 nonviremic) from January 2018 to September 2019, according to Bashar Aqel, MD, of the Mayo Clinic, Phoenix, Ariz., and colleagues.

Seven of the grafts were obtained from donation after cardiac death (DCD). Six recipients underwent simultaneous liver/kidney (SLK) transplant, and four patients were repeat liver transplants.
 

Sustained viral response

None of the recipients of an HCV nonviremic graft developed HCV viremia. However, all 20 patients who received HCV viremic grafts had HCV viremia confirmed within 3 days after liver transplant. Direct-acting antiviral (DAA) treatment was started at the median time of 27.5 days in these patients.

All 20 patients successfully completed the treatment and achieved a sustained viral response. In addition, the DAA treatment was well tolerated with minimal adverse events, according to the researchers.

However, one patient died, having developed HCV-related acute membranous nephropathy that resulted in end-stage kidney disease. In addition, a recipient of an HCV nonviremic graft died with acute myocardial infarction 610 days post liver transplant, the authors reported.

“This multicenter study demonstrated LT [liver transplantation] using HCV-seropositive grafts to HCV-seronegative recipients resulted in acceptable short-term outcomes even with the use of DCD grafts and expansion into SLK or repeat LT. However, a careful ongoing assessment regarding patient and graft selection, complications, and the timing of treatment is required,” the researchers concluded.

The study was funded in part by the McIver Estate Young Investigator Benefactor Award. The authors reported they had no potential conflicts.

mlesney@mdedge.com

SOURCE: Aqel B et al. J Hepatol. 2020, Nov 11. doi: 10.1016/j.jhep.2020.11.005.

In patients with T-cell lymphoma, allogeneic transplant can lead to durable remissions among patients who might otherwise have poor outcomes, results of a large retrospective observational study suggest.

Five-year progression-free survival (PFS) approached 40% and 5-year overall survival (OS) was over 50% in the study, which according to an investigator is the largest-ever reported patient series of allogeneic stem cell transplantation in T-cell lymphomas.

“We believe that eligible patients with relapsed/refractory T-cell lymphomas should be considered for consultation for allogeneic transplant by an expert clinician,” said investigator Neha Mehta-Shah, MD, of Washington University in St. Louis.

“These decisions should occur on a patient by patient level – but it’s important to consider this,” Dr. Mehta-Shah said at the annual meeting of the American Society of Hematology, held virtually this year.

Notably, patients with cutaneous T-cell lymphoma (CTCL) had a higher rate of relapse yet similar overall survival (OS) compared to patients with common peripheral T-cell lymphoma (PTCL) subtypes, according to Dr. Mehta-Shah.

Among PTCL subtypes, there was a trend toward improved PFS and OS for angioimmunoblastic T-cell lymphoma (AITL), compared with PTCL not otherwise specified (PTCL-NOS) and anaplastic large-cell lymphoma (ALCL), she added.

Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center, said the results of this retrospective study need to considered in light of the treatment-related risks associated with allogeneic transplantation.

Treatment-related mortality in the study ranged from about 8% to 24%, depending on the donor type, while acute and chronic graft-versus-host-disease (GvHD) was seen in more than 40% of patients, the reported data show.

“If I have a relapsed patient with AITL, I would look to this data and say that patients with AITL appear in a retrospective study to have a strong benefit,” Dr. Diefenbach said in an interview.

“For the other patients, you would describe both potential benefits and also discuss the treatment-associated risks – both the chronic GvHD and transplant-related mortality – and you’d have to balance the risk with the benefits for each individual case,” Dr. Diefenbach added.

The retrospective analysis by Dr. Mehta-Shah and colleagues included 508 consecutive T-cell lymphoma patients receiving allogeneic transplants at 12 academic centers between 2000 and 2019. The most common subtypes were PTCL-NOS in 26%, AITL in 16%, CTCL in 13%, and hepatosplenic T-cell lymphoma (HSTCL) in 7%. About 40% had a matched related donor (MRD) and 39% had a matched unrelated donor (MUD). The conditioning regimen was myeloablative in about a third of patients and nonmyeloablative in two-thirds.

At 5 years, PFS was 39.4% and OS was 50.8% for the overall study cohort, Dr. Mehta-Shah reported, noting that the median time from relapse to death post allogeneic transplant was 10.2 months.

Patients in complete remission at the time of transplant fared better than others, with a median PFS of 44.6 months vs. 8.5 months for those in partial remission, 21.0 months in those with stable disease, and 3.5 months for those with progressive disease at time of transplant, data show.

Patients with common PTCL subtypes had better PFS compared to patients with CTCL, yet OS was similar, according to the investigator. At 5 years, PFS was 43.7% and 18.6%, respectively, for PTCL and CTCL, while OS was 53.1% and 44.0%, respectively.

There was a trend toward improved outcomes for AITL relative to PTCL-NOS and ALCL, with a median PFS of 51.4 months for AITL versus 18.3 months those other subtypes. Similarly, median OS was not reached for AITL versus 73.1 months in the other subtypes.

Treatment-related mortality was lowest for patients with MRDs, or 8.2% at 12 months, Dr. Mehta-Shah reported, while patients with MUDs, mismatched donors, or haploidentical donors had treatment-related mortality of 13% to 16% at 12 months, and those with cord blood donors had treatment-related mortality of nearly 24% at 12 months.

Acute GvHD was observed in 46% of patients and chronic GvHD was seen in nearly 41%, the investigator added.

While these findings are important to consider in individual patient consultations, the study is nevertheless subject to limitations including patient selection and referral bias, according to Dr. Mehta-Shah.

“This was a retrospective analysis of patients who underwent transplant,” she said in a question-and-answer period. “Of course, that is heavily biased by who got to a transplant center, who was well enough to achieve transplant, and who had a donor or donor options, as well as their overall health and depth of remission,” the researcher said.

“I think this just represents what we could tell patients about what may happen to them once they embark on a transplant,” she added, “but really, there would be more prospective work needed to be done for what happens to patients overarching, and how many of them even get to a transplant consultation.”

Further studies should be done to develop predictive tools or biomarkers to determine who benefits from an allogeneic transplant, if there are predictors of relapse following allogeneic transplant, and what are the mechanisms of relapse following allogeneic transplant, according to Dr. Mehta-Shah.

Dr. Mehta-Shah reported research funding from Bristol Myers-Squibb, Celgene, Verastem, Corvus, Innate Pharmaceuticals, and Genentech/Roche. She reported consultancy with Kyowa Hakko Kirin, C4 Therapeutics, and Karyopharm Therapeutics.
 

SOURCE: Mehta-Shah N et al. ASH 2020, Abstract 41.

In patients with T-cell lymphoma, allogeneic transplant can lead to durable remissions among patients who might otherwise have poor outcomes, results of a large retrospective observational study suggest.

Five-year progression-free survival (PFS) approached 40% and 5-year overall survival (OS) was over 50% in the study, which according to an investigator is the largest-ever reported patient series of allogeneic stem cell transplantation in T-cell lymphomas.

“We believe that eligible patients with relapsed/refractory T-cell lymphomas should be considered for consultation for allogeneic transplant by an expert clinician,” said investigator Neha Mehta-Shah, MD, of Washington University in St. Louis.

“These decisions should occur on a patient by patient level – but it’s important to consider this,” Dr. Mehta-Shah said at the annual meeting of the American Society of Hematology, held virtually this year.

Notably, patients with cutaneous T-cell lymphoma (CTCL) had a higher rate of relapse yet similar overall survival (OS) compared to patients with common peripheral T-cell lymphoma (PTCL) subtypes, according to Dr. Mehta-Shah.

Among PTCL subtypes, there was a trend toward improved PFS and OS for angioimmunoblastic T-cell lymphoma (AITL), compared with PTCL not otherwise specified (PTCL-NOS) and anaplastic large-cell lymphoma (ALCL), she added.

Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center, said the results of this retrospective study need to considered in light of the treatment-related risks associated with allogeneic transplantation.

Treatment-related mortality in the study ranged from about 8% to 24%, depending on the donor type, while acute and chronic graft-versus-host-disease (GvHD) was seen in more than 40% of patients, the reported data show.

“If I have a relapsed patient with AITL, I would look to this data and say that patients with AITL appear in a retrospective study to have a strong benefit,” Dr. Diefenbach said in an interview.

“For the other patients, you would describe both potential benefits and also discuss the treatment-associated risks – both the chronic GvHD and transplant-related mortality – and you’d have to balance the risk with the benefits for each individual case,” Dr. Diefenbach added.

The retrospective analysis by Dr. Mehta-Shah and colleagues included 508 consecutive T-cell lymphoma patients receiving allogeneic transplants at 12 academic centers between 2000 and 2019. The most common subtypes were PTCL-NOS in 26%, AITL in 16%, CTCL in 13%, and hepatosplenic T-cell lymphoma (HSTCL) in 7%. About 40% had a matched related donor (MRD) and 39% had a matched unrelated donor (MUD). The conditioning regimen was myeloablative in about a third of patients and nonmyeloablative in two-thirds.

At 5 years, PFS was 39.4% and OS was 50.8% for the overall study cohort, Dr. Mehta-Shah reported, noting that the median time from relapse to death post allogeneic transplant was 10.2 months.

Patients in complete remission at the time of transplant fared better than others, with a median PFS of 44.6 months vs. 8.5 months for those in partial remission, 21.0 months in those with stable disease, and 3.5 months for those with progressive disease at time of transplant, data show.

Patients with common PTCL subtypes had better PFS compared to patients with CTCL, yet OS was similar, according to the investigator. At 5 years, PFS was 43.7% and 18.6%, respectively, for PTCL and CTCL, while OS was 53.1% and 44.0%, respectively.

There was a trend toward improved outcomes for AITL relative to PTCL-NOS and ALCL, with a median PFS of 51.4 months for AITL versus 18.3 months those other subtypes. Similarly, median OS was not reached for AITL versus 73.1 months in the other subtypes.

Treatment-related mortality was lowest for patients with MRDs, or 8.2% at 12 months, Dr. Mehta-Shah reported, while patients with MUDs, mismatched donors, or haploidentical donors had treatment-related mortality of 13% to 16% at 12 months, and those with cord blood donors had treatment-related mortality of nearly 24% at 12 months.

Acute GvHD was observed in 46% of patients and chronic GvHD was seen in nearly 41%, the investigator added.

While these findings are important to consider in individual patient consultations, the study is nevertheless subject to limitations including patient selection and referral bias, according to Dr. Mehta-Shah.

“This was a retrospective analysis of patients who underwent transplant,” she said in a question-and-answer period. “Of course, that is heavily biased by who got to a transplant center, who was well enough to achieve transplant, and who had a donor or donor options, as well as their overall health and depth of remission,” the researcher said.

“I think this just represents what we could tell patients about what may happen to them once they embark on a transplant,” she added, “but really, there would be more prospective work needed to be done for what happens to patients overarching, and how many of them even get to a transplant consultation.”

Further studies should be done to develop predictive tools or biomarkers to determine who benefits from an allogeneic transplant, if there are predictors of relapse following allogeneic transplant, and what are the mechanisms of relapse following allogeneic transplant, according to Dr. Mehta-Shah.

Dr. Mehta-Shah reported research funding from Bristol Myers-Squibb, Celgene, Verastem, Corvus, Innate Pharmaceuticals, and Genentech/Roche. She reported consultancy with Kyowa Hakko Kirin, C4 Therapeutics, and Karyopharm Therapeutics.
 

SOURCE: Mehta-Shah N et al. ASH 2020, Abstract 41.

In patients with T-cell lymphoma, allogeneic transplant can lead to durable remissions among patients who might otherwise have poor outcomes, results of a large retrospective observational study suggest.

Five-year progression-free survival (PFS) approached 40% and 5-year overall survival (OS) was over 50% in the study, which according to an investigator is the largest-ever reported patient series of allogeneic stem cell transplantation in T-cell lymphomas.

“We believe that eligible patients with relapsed/refractory T-cell lymphomas should be considered for consultation for allogeneic transplant by an expert clinician,” said investigator Neha Mehta-Shah, MD, of Washington University in St. Louis.

“These decisions should occur on a patient by patient level – but it’s important to consider this,” Dr. Mehta-Shah said at the annual meeting of the American Society of Hematology, held virtually this year.

Notably, patients with cutaneous T-cell lymphoma (CTCL) had a higher rate of relapse yet similar overall survival (OS) compared to patients with common peripheral T-cell lymphoma (PTCL) subtypes, according to Dr. Mehta-Shah.

Among PTCL subtypes, there was a trend toward improved PFS and OS for angioimmunoblastic T-cell lymphoma (AITL), compared with PTCL not otherwise specified (PTCL-NOS) and anaplastic large-cell lymphoma (ALCL), she added.

Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center, said the results of this retrospective study need to considered in light of the treatment-related risks associated with allogeneic transplantation.

Treatment-related mortality in the study ranged from about 8% to 24%, depending on the donor type, while acute and chronic graft-versus-host-disease (GvHD) was seen in more than 40% of patients, the reported data show.

“If I have a relapsed patient with AITL, I would look to this data and say that patients with AITL appear in a retrospective study to have a strong benefit,” Dr. Diefenbach said in an interview.

“For the other patients, you would describe both potential benefits and also discuss the treatment-associated risks – both the chronic GvHD and transplant-related mortality – and you’d have to balance the risk with the benefits for each individual case,” Dr. Diefenbach added.

The retrospective analysis by Dr. Mehta-Shah and colleagues included 508 consecutive T-cell lymphoma patients receiving allogeneic transplants at 12 academic centers between 2000 and 2019. The most common subtypes were PTCL-NOS in 26%, AITL in 16%, CTCL in 13%, and hepatosplenic T-cell lymphoma (HSTCL) in 7%. About 40% had a matched related donor (MRD) and 39% had a matched unrelated donor (MUD). The conditioning regimen was myeloablative in about a third of patients and nonmyeloablative in two-thirds.

At 5 years, PFS was 39.4% and OS was 50.8% for the overall study cohort, Dr. Mehta-Shah reported, noting that the median time from relapse to death post allogeneic transplant was 10.2 months.

Patients in complete remission at the time of transplant fared better than others, with a median PFS of 44.6 months vs. 8.5 months for those in partial remission, 21.0 months in those with stable disease, and 3.5 months for those with progressive disease at time of transplant, data show.

Patients with common PTCL subtypes had better PFS compared to patients with CTCL, yet OS was similar, according to the investigator. At 5 years, PFS was 43.7% and 18.6%, respectively, for PTCL and CTCL, while OS was 53.1% and 44.0%, respectively.

There was a trend toward improved outcomes for AITL relative to PTCL-NOS and ALCL, with a median PFS of 51.4 months for AITL versus 18.3 months those other subtypes. Similarly, median OS was not reached for AITL versus 73.1 months in the other subtypes.

Treatment-related mortality was lowest for patients with MRDs, or 8.2% at 12 months, Dr. Mehta-Shah reported, while patients with MUDs, mismatched donors, or haploidentical donors had treatment-related mortality of 13% to 16% at 12 months, and those with cord blood donors had treatment-related mortality of nearly 24% at 12 months.

Acute GvHD was observed in 46% of patients and chronic GvHD was seen in nearly 41%, the investigator added.

While these findings are important to consider in individual patient consultations, the study is nevertheless subject to limitations including patient selection and referral bias, according to Dr. Mehta-Shah.

“This was a retrospective analysis of patients who underwent transplant,” she said in a question-and-answer period. “Of course, that is heavily biased by who got to a transplant center, who was well enough to achieve transplant, and who had a donor or donor options, as well as their overall health and depth of remission,” the researcher said.

“I think this just represents what we could tell patients about what may happen to them once they embark on a transplant,” she added, “but really, there would be more prospective work needed to be done for what happens to patients overarching, and how many of them even get to a transplant consultation.”

Further studies should be done to develop predictive tools or biomarkers to determine who benefits from an allogeneic transplant, if there are predictors of relapse following allogeneic transplant, and what are the mechanisms of relapse following allogeneic transplant, according to Dr. Mehta-Shah.

Dr. Mehta-Shah reported research funding from Bristol Myers-Squibb, Celgene, Verastem, Corvus, Innate Pharmaceuticals, and Genentech/Roche. She reported consultancy with Kyowa Hakko Kirin, C4 Therapeutics, and Karyopharm Therapeutics.
 

SOURCE: Mehta-Shah N et al. ASH 2020, Abstract 41.

Can receiving all posttransplant care at home improve outcomes for patients undergoing hematopoietic stem cell transplant (HSCT)? Researchers are conducting phase 2 trials to find out.

Anthony D. Sung, MD, of Duke University, Durham, N.C., described this research to David H. Henry, MD, of Penn Medicine in Philadelphia, host of the Blood & Cancer podcast.

On the Nov. 12 episode of Blood & Cancer, Dr. Sung outlined the process of receiving post-HSCT care at home and discussed Duke’s clinical trials assessing the impact of home care on costs, quality of life, the microbiome, graft-versus-host disease (GVHD), and other outcomes. The following transcript of that discussion has been edited for length and clarity.
 

David Henry, MD: Welcome to this podcast. We’re delighted to have you listening today because we’re going to be speaking with Dr. Anthony Sung from Duke University, where he is assistant professor of medicine in the division of hematologic malignancies and cellular therapies.

So let’s get right into it. I’m a generalist at Pennsylvania Hospital in Philadelphia, where we do auto [autologous] transplants at the main university hospital, autos and allos [allogeneic], and these patients are in [hospital] anywhere from a little bit to a long time. And I’ve often thought to try and do some of this as outpatient. But I think you have a project, which I’m going to ask you to describe, where you try and do most [treatment] outpatient. So tell me what this project is all about, and we’ll skip through how it works.
 

Anthony Sung, MD: Absolutely. So this is focused on both autologous as well as allogeneic stem cell transplant patients at Duke and a few other centers around the country. Duke University has actually had a long history of an outpatient transplant program. This program is based in a day hospital, which is basically like a high-functioning clinic that’s open 7 days a week. Patients can come into the hospital and receive blood transfusions, IV infusions, and any other therapies that they would need as part of their stem cell transplant treatment in the outpatient setting, returning to their home or to a furnished apartment, temporary lodging, while they’re receiving their care.

What we have done, however, is to take this a step further and deliver care within the patient’s own home. In a sense, we’re returning to an older form of medicine where doctors would make house calls. Within our home-transplant program, instead of the patients having to be in the hospital or instead of having to come back and forth to the outpatient hospital every day, which places additional stresses and strains upon them, our providers will make house calls to the patient’s homes, will draw their labs right there, do a history and physical exam, assess and attend to any of the needs that they have.

Then in the afternoon, the providers will return, have the labs run in the hospital, as they would normally do, a CBC, CMP [comprehensive metabolic panel], and so forth. And then a nurse would return to the patient’s home if needed to deliver any interventions, such as blood transfusions, intravenous fluids, or electrolytes, right there in the comfort of the patient’s own home.
 

Dr. Henry: So let’s then take it through what happens. Say I am a patient with myeloma. I’ve had various therapies, and it’s time for me to get an autotransplant, let’s say. And so I need to do a couple of things. I need to get my stem cells collected. I need to then get my high-dose [conditioning] therapy, and then follows the stem cell therapy reinfusion. So can you take me through each step? Where is that done?

Dr. Sung: Absolutely. So the collection will occur in the outpatient setting, typically after mobilization with G-CSF [granulocyte colony–stimulating factor] and/or plerixafor. That will occur in our outpatient clinic with one of our leukapheresis machines. And the patient will then return to that same outpatient clinic, which is the same building, the same facility as the hospital, to receive melphalan conditioning. And then, following conditioning, about 24 hours after, day 0, that’s the day of their stem cell transplant infusion, which we do in the hospital setting just because of the potential for reactions associated with that.

But everything after that, from day 1 onwards, we try to keep them at home. And as I said, they will stay in their home. One of our nurse practitioners or physician assistants will visit them in the morning, do the assessment and draw the labs. And nurses will return in the afternoon to deliver any supportive care that they need.
 

Dr. Henry: So let’s define “home.” So I’m a Philadelphia resident and I say to you, Dr. Sung, I want to go home. You say, well, Philadelphia is too far. What is close enough and not too far, when you say home?

Dr. Sung: Absolutely. So when we originally conceived the program, we focused on patients who lived within an hour of our transplant center. And in part, that was because, as you know, unfortunately, things can sometimes go wrong during transplant. One of the most concerning ones is infections. And if a patient were to develop a neutropenic fever, we would want them to be seen as urgently as possible within an hour. And that’s where our limitation comes from.

So for our patients who live more than an hour away, those are the ones that we will have relocate to temporary lodging near our transplant center. And we’ve worked with several facilities in the area that have clean, furnished units that are available for rent. Many insurances also include lodging benefits for patients during stem cell transplant, recognizing this need. And historically, those [patients] were not considered part of our transplant patient cohorts.

I have not mentioned, but we initially did this in a phase 1 study, and we’re now studying it in a series of randomized, phase 2 studies that I can go into detail later on. And because they were not necessarily in their home, but a temporary lodging environment, those patients who relocated to Durham were not eligible for a home transplant study.

However, in the setting of the COVID-19 pandemic, we’ve actually pivoted our program in many ways. Specifically, if you think about a patient who’s coming into contact with the medical system, they come to the hospital, they meet someone at the door who is screening them for COVID-19. They see someone who checks them in at the front desk. A medical assistant takes them in the back. Someone calls their labs and phlebotomy. They may encounter other patients and environmental services, other individuals in the setting. You’re talking about dozens of different encounters. Who knows how many surfaces that potentially someone with COVID-19 has coughed on or contaminated?

And in contrast, you have house calls, which even if they are located in the temporary lodging, that’s just one or two individuals going into their living environment. They’re not encountering any different surfaces. And so, in the setting of COVID-19, we felt that this platform had the potential to help protect all our transplant patients who are among the most vulnerable patients, the most immunocompromised patients, and so we expanded our program to include those individuals as well.
 

Dr. Henry: So ... what are the actual outcomes of your patients in terms of how they’re doing, engrafting, and getting cured of their malignancy?

Dr. Sung: So as I mentioned, we first did this in a phase 1 safety and feasibility pilot study of both autologous and allo-transplant patients. This was presented at the annual meeting of the American Society of Hematology [Blood. 2017;130:745]. And we’re actually about ready to submit our manuscript on this.

And we found no difference in outcomes between patients who received care in the home transplant setting versus those who received conventional care either in the day hospital or hospital environment. The process appeared safe. Patients did just as well, if not better. Certainly, anecdotally, patients would talk about feeling so much more comfortable and happier being cared for in that home environment.

And we are now in the process of formally studying these outcomes in two NIH [National Institutes of Health]-funded clinical trials, one focused on allogeneic transplant patients [NCT02218151] and the other focused on autologous transplant patients [NCT01725022].
 

Dr. Henry: So of course, I’m waiting for this next question, which is cost. The services are the same, but you have people traveling, people who are highly skilled caregivers. Have you looked at cost differences from hospital versus home?

Dr. Sung: Absolutely. So you do have increased upfront costs because you have travel time for advanced practice providers and nurses. Not only that, but when a nurse is helping to give a patient a blood transfusion in the home environment, they’re 1:1 with that patient as opposed to the day hospital where a nurse could help with transfusions simultaneously for multiple patients. At the same time, by keeping patients out of the hospital, you have drastic, significant cost savings in that way.

In addition, I should mention, part of why we’re conducting these randomized, phase 2 clinical trials is we believe home care actually has the potential to decrease complications. One area of my research is on the impact of the microbiome, the bacteria in the gut, on transplant outcomes. And we’ve done a number of studies, many in collaboration with Memorial Sloan Kettering, showing that disruption of the microbiota, the bacteria in the gut, is associated with increased infections, graft-versus-host disease, and treatment-related mortality if we’re able to keep patients in their home setting.

However, I actually should go back a step. It’s well known that, if you take an individual from their home setting and put them in a foreign environment such as the hospital, that new environment, that new diet, hospital food as opposed to home food, and so forth, can dramatically shift the microbiome. Our hypothesis is that, by keeping patients in the home environment, their familiar environment will be able to help preserve their microbiome, thus decreasing infections, graft-versus-host disease, and other complications. That’s actually the goal of our studies: to see if we can preserve the microbiome and decrease complications.
 

Dr. Henry: So how will you evaluate that? Are you doing fecal studies, patient culture studies? How are you testing that?

Dr. Sung: So we have a very broad biobank program where we collect stool on our transplantations, pretransplant, day 0, weekly for the first month. And then, in the case of our allogeneic transplant patients, day 60, 90, 180, and 365.

And we do that both in our home transplant patients as well as their matched controls on the phase 2 studies. And we also collect it on a lot of our other transplant patients as part of our biobanking programs and our observational studies to try to understand what’s going on during transplant and how to help improve transplant outcomes.
 

Dr. Henry: Do you have any results of that? You’re probably showing a difference.

Dr. Sung: We think so, on some preliminary results, but those were based on small numbers of patients. And we’re really hoping that these randomized clinical trials with the larger numbers of patients enrolled will help show that difference.

But getting back to your earlier question about cost, a case of graft-versus-host disease, grade 2 or higher, can add about $100,000 to the cost of care. So if you prevent one case of bad gut or liver graft-versus-host disease, those are your cost savings right there.

The randomized, phase 2 trial for allogeneic transplant patients, the primary endpoint is graft-versus-host disease. So we’re looking at the microbiome and those associations and the prevention of GVHD. For the randomized clinical trial in autologous transplant patients – with autologous stem cells, you’re not going to get GVHD – but we do hope to improve quality of life and long-term outcomes in those patients as well.
 

Dr. Henry: Wonderful. Well, Tony, I really want to thank you so much for talking with us today.

Dr. Sung: Thank you very much for this opportunity. And again, I also want to just thank everyone who’s been involved in these studies, the advanced practice providers and nurses who are caring for our patients at home, the study staff who have been involved. Particularly, I’d like to highlight the role of both Nelson Chao, who’s our division chief and my mentor who piloted and first developed home transplant, and Kristin Nichols, our research nurse who has really led the drive forward.

Dr. Sung and Dr. Henry have no relevant disclosures. The trials are funded by grants from the National Institutes of Health.

Can receiving all posttransplant care at home improve outcomes for patients undergoing hematopoietic stem cell transplant (HSCT)? Researchers are conducting phase 2 trials to find out.

Anthony D. Sung, MD, of Duke University, Durham, N.C., described this research to David H. Henry, MD, of Penn Medicine in Philadelphia, host of the Blood & Cancer podcast.

On the Nov. 12 episode of Blood & Cancer, Dr. Sung outlined the process of receiving post-HSCT care at home and discussed Duke’s clinical trials assessing the impact of home care on costs, quality of life, the microbiome, graft-versus-host disease (GVHD), and other outcomes. The following transcript of that discussion has been edited for length and clarity.
 

David Henry, MD: Welcome to this podcast. We’re delighted to have you listening today because we’re going to be speaking with Dr. Anthony Sung from Duke University, where he is assistant professor of medicine in the division of hematologic malignancies and cellular therapies.

So let’s get right into it. I’m a generalist at Pennsylvania Hospital in Philadelphia, where we do auto [autologous] transplants at the main university hospital, autos and allos [allogeneic], and these patients are in [hospital] anywhere from a little bit to a long time. And I’ve often thought to try and do some of this as outpatient. But I think you have a project, which I’m going to ask you to describe, where you try and do most [treatment] outpatient. So tell me what this project is all about, and we’ll skip through how it works.
 

Anthony Sung, MD: Absolutely. So this is focused on both autologous as well as allogeneic stem cell transplant patients at Duke and a few other centers around the country. Duke University has actually had a long history of an outpatient transplant program. This program is based in a day hospital, which is basically like a high-functioning clinic that’s open 7 days a week. Patients can come into the hospital and receive blood transfusions, IV infusions, and any other therapies that they would need as part of their stem cell transplant treatment in the outpatient setting, returning to their home or to a furnished apartment, temporary lodging, while they’re receiving their care.

What we have done, however, is to take this a step further and deliver care within the patient’s own home. In a sense, we’re returning to an older form of medicine where doctors would make house calls. Within our home-transplant program, instead of the patients having to be in the hospital or instead of having to come back and forth to the outpatient hospital every day, which places additional stresses and strains upon them, our providers will make house calls to the patient’s homes, will draw their labs right there, do a history and physical exam, assess and attend to any of the needs that they have.

Then in the afternoon, the providers will return, have the labs run in the hospital, as they would normally do, a CBC, CMP [comprehensive metabolic panel], and so forth. And then a nurse would return to the patient’s home if needed to deliver any interventions, such as blood transfusions, intravenous fluids, or electrolytes, right there in the comfort of the patient’s own home.
 

Dr. Henry: So let’s then take it through what happens. Say I am a patient with myeloma. I’ve had various therapies, and it’s time for me to get an autotransplant, let’s say. And so I need to do a couple of things. I need to get my stem cells collected. I need to then get my high-dose [conditioning] therapy, and then follows the stem cell therapy reinfusion. So can you take me through each step? Where is that done?

Dr. Sung: Absolutely. So the collection will occur in the outpatient setting, typically after mobilization with G-CSF [granulocyte colony–stimulating factor] and/or plerixafor. That will occur in our outpatient clinic with one of our leukapheresis machines. And the patient will then return to that same outpatient clinic, which is the same building, the same facility as the hospital, to receive melphalan conditioning. And then, following conditioning, about 24 hours after, day 0, that’s the day of their stem cell transplant infusion, which we do in the hospital setting just because of the potential for reactions associated with that.

But everything after that, from day 1 onwards, we try to keep them at home. And as I said, they will stay in their home. One of our nurse practitioners or physician assistants will visit them in the morning, do the assessment and draw the labs. And nurses will return in the afternoon to deliver any supportive care that they need.
 

Dr. Henry: So let’s define “home.” So I’m a Philadelphia resident and I say to you, Dr. Sung, I want to go home. You say, well, Philadelphia is too far. What is close enough and not too far, when you say home?

Dr. Sung: Absolutely. So when we originally conceived the program, we focused on patients who lived within an hour of our transplant center. And in part, that was because, as you know, unfortunately, things can sometimes go wrong during transplant. One of the most concerning ones is infections. And if a patient were to develop a neutropenic fever, we would want them to be seen as urgently as possible within an hour. And that’s where our limitation comes from.

So for our patients who live more than an hour away, those are the ones that we will have relocate to temporary lodging near our transplant center. And we’ve worked with several facilities in the area that have clean, furnished units that are available for rent. Many insurances also include lodging benefits for patients during stem cell transplant, recognizing this need. And historically, those [patients] were not considered part of our transplant patient cohorts.

I have not mentioned, but we initially did this in a phase 1 study, and we’re now studying it in a series of randomized, phase 2 studies that I can go into detail later on. And because they were not necessarily in their home, but a temporary lodging environment, those patients who relocated to Durham were not eligible for a home transplant study.

However, in the setting of the COVID-19 pandemic, we’ve actually pivoted our program in many ways. Specifically, if you think about a patient who’s coming into contact with the medical system, they come to the hospital, they meet someone at the door who is screening them for COVID-19. They see someone who checks them in at the front desk. A medical assistant takes them in the back. Someone calls their labs and phlebotomy. They may encounter other patients and environmental services, other individuals in the setting. You’re talking about dozens of different encounters. Who knows how many surfaces that potentially someone with COVID-19 has coughed on or contaminated?

And in contrast, you have house calls, which even if they are located in the temporary lodging, that’s just one or two individuals going into their living environment. They’re not encountering any different surfaces. And so, in the setting of COVID-19, we felt that this platform had the potential to help protect all our transplant patients who are among the most vulnerable patients, the most immunocompromised patients, and so we expanded our program to include those individuals as well.
 

Dr. Henry: So ... what are the actual outcomes of your patients in terms of how they’re doing, engrafting, and getting cured of their malignancy?

Dr. Sung: So as I mentioned, we first did this in a phase 1 safety and feasibility pilot study of both autologous and allo-transplant patients. This was presented at the annual meeting of the American Society of Hematology [Blood. 2017;130:745]. And we’re actually about ready to submit our manuscript on this.

And we found no difference in outcomes between patients who received care in the home transplant setting versus those who received conventional care either in the day hospital or hospital environment. The process appeared safe. Patients did just as well, if not better. Certainly, anecdotally, patients would talk about feeling so much more comfortable and happier being cared for in that home environment.

And we are now in the process of formally studying these outcomes in two NIH [National Institutes of Health]-funded clinical trials, one focused on allogeneic transplant patients [NCT02218151] and the other focused on autologous transplant patients [NCT01725022].
 

Dr. Henry: So of course, I’m waiting for this next question, which is cost. The services are the same, but you have people traveling, people who are highly skilled caregivers. Have you looked at cost differences from hospital versus home?

Dr. Sung: Absolutely. So you do have increased upfront costs because you have travel time for advanced practice providers and nurses. Not only that, but when a nurse is helping to give a patient a blood transfusion in the home environment, they’re 1:1 with that patient as opposed to the day hospital where a nurse could help with transfusions simultaneously for multiple patients. At the same time, by keeping patients out of the hospital, you have drastic, significant cost savings in that way.

In addition, I should mention, part of why we’re conducting these randomized, phase 2 clinical trials is we believe home care actually has the potential to decrease complications. One area of my research is on the impact of the microbiome, the bacteria in the gut, on transplant outcomes. And we’ve done a number of studies, many in collaboration with Memorial Sloan Kettering, showing that disruption of the microbiota, the bacteria in the gut, is associated with increased infections, graft-versus-host disease, and treatment-related mortality if we’re able to keep patients in their home setting.

However, I actually should go back a step. It’s well known that, if you take an individual from their home setting and put them in a foreign environment such as the hospital, that new environment, that new diet, hospital food as opposed to home food, and so forth, can dramatically shift the microbiome. Our hypothesis is that, by keeping patients in the home environment, their familiar environment will be able to help preserve their microbiome, thus decreasing infections, graft-versus-host disease, and other complications. That’s actually the goal of our studies: to see if we can preserve the microbiome and decrease complications.
 

Dr. Henry: So how will you evaluate that? Are you doing fecal studies, patient culture studies? How are you testing that?

Dr. Sung: So we have a very broad biobank program where we collect stool on our transplantations, pretransplant, day 0, weekly for the first month. And then, in the case of our allogeneic transplant patients, day 60, 90, 180, and 365.

And we do that both in our home transplant patients as well as their matched controls on the phase 2 studies. And we also collect it on a lot of our other transplant patients as part of our biobanking programs and our observational studies to try to understand what’s going on during transplant and how to help improve transplant outcomes.
 

Dr. Henry: Do you have any results of that? You’re probably showing a difference.

Dr. Sung: We think so, on some preliminary results, but those were based on small numbers of patients. And we’re really hoping that these randomized clinical trials with the larger numbers of patients enrolled will help show that difference.

But getting back to your earlier question about cost, a case of graft-versus-host disease, grade 2 or higher, can add about $100,000 to the cost of care. So if you prevent one case of bad gut or liver graft-versus-host disease, those are your cost savings right there.

The randomized, phase 2 trial for allogeneic transplant patients, the primary endpoint is graft-versus-host disease. So we’re looking at the microbiome and those associations and the prevention of GVHD. For the randomized clinical trial in autologous transplant patients – with autologous stem cells, you’re not going to get GVHD – but we do hope to improve quality of life and long-term outcomes in those patients as well.
 

Dr. Henry: Wonderful. Well, Tony, I really want to thank you so much for talking with us today.

Dr. Sung: Thank you very much for this opportunity. And again, I also want to just thank everyone who’s been involved in these studies, the advanced practice providers and nurses who are caring for our patients at home, the study staff who have been involved. Particularly, I’d like to highlight the role of both Nelson Chao, who’s our division chief and my mentor who piloted and first developed home transplant, and Kristin Nichols, our research nurse who has really led the drive forward.

Dr. Sung and Dr. Henry have no relevant disclosures. The trials are funded by grants from the National Institutes of Health.

Can receiving all posttransplant care at home improve outcomes for patients undergoing hematopoietic stem cell transplant (HSCT)? Researchers are conducting phase 2 trials to find out.

Anthony D. Sung, MD, of Duke University, Durham, N.C., described this research to David H. Henry, MD, of Penn Medicine in Philadelphia, host of the Blood & Cancer podcast.

On the Nov. 12 episode of Blood & Cancer, Dr. Sung outlined the process of receiving post-HSCT care at home and discussed Duke’s clinical trials assessing the impact of home care on costs, quality of life, the microbiome, graft-versus-host disease (GVHD), and other outcomes. The following transcript of that discussion has been edited for length and clarity.
 

David Henry, MD: Welcome to this podcast. We’re delighted to have you listening today because we’re going to be speaking with Dr. Anthony Sung from Duke University, where he is assistant professor of medicine in the division of hematologic malignancies and cellular therapies.

So let’s get right into it. I’m a generalist at Pennsylvania Hospital in Philadelphia, where we do auto [autologous] transplants at the main university hospital, autos and allos [allogeneic], and these patients are in [hospital] anywhere from a little bit to a long time. And I’ve often thought to try and do some of this as outpatient. But I think you have a project, which I’m going to ask you to describe, where you try and do most [treatment] outpatient. So tell me what this project is all about, and we’ll skip through how it works.
 

Anthony Sung, MD: Absolutely. So this is focused on both autologous as well as allogeneic stem cell transplant patients at Duke and a few other centers around the country. Duke University has actually had a long history of an outpatient transplant program. This program is based in a day hospital, which is basically like a high-functioning clinic that’s open 7 days a week. Patients can come into the hospital and receive blood transfusions, IV infusions, and any other therapies that they would need as part of their stem cell transplant treatment in the outpatient setting, returning to their home or to a furnished apartment, temporary lodging, while they’re receiving their care.

What we have done, however, is to take this a step further and deliver care within the patient’s own home. In a sense, we’re returning to an older form of medicine where doctors would make house calls. Within our home-transplant program, instead of the patients having to be in the hospital or instead of having to come back and forth to the outpatient hospital every day, which places additional stresses and strains upon them, our providers will make house calls to the patient’s homes, will draw their labs right there, do a history and physical exam, assess and attend to any of the needs that they have.

Then in the afternoon, the providers will return, have the labs run in the hospital, as they would normally do, a CBC, CMP [comprehensive metabolic panel], and so forth. And then a nurse would return to the patient’s home if needed to deliver any interventions, such as blood transfusions, intravenous fluids, or electrolytes, right there in the comfort of the patient’s own home.
 

Dr. Henry: So let’s then take it through what happens. Say I am a patient with myeloma. I’ve had various therapies, and it’s time for me to get an autotransplant, let’s say. And so I need to do a couple of things. I need to get my stem cells collected. I need to then get my high-dose [conditioning] therapy, and then follows the stem cell therapy reinfusion. So can you take me through each step? Where is that done?

Dr. Sung: Absolutely. So the collection will occur in the outpatient setting, typically after mobilization with G-CSF [granulocyte colony–stimulating factor] and/or plerixafor. That will occur in our outpatient clinic with one of our leukapheresis machines. And the patient will then return to that same outpatient clinic, which is the same building, the same facility as the hospital, to receive melphalan conditioning. And then, following conditioning, about 24 hours after, day 0, that’s the day of their stem cell transplant infusion, which we do in the hospital setting just because of the potential for reactions associated with that.

But everything after that, from day 1 onwards, we try to keep them at home. And as I said, they will stay in their home. One of our nurse practitioners or physician assistants will visit them in the morning, do the assessment and draw the labs. And nurses will return in the afternoon to deliver any supportive care that they need.
 

Dr. Henry: So let’s define “home.” So I’m a Philadelphia resident and I say to you, Dr. Sung, I want to go home. You say, well, Philadelphia is too far. What is close enough and not too far, when you say home?

Dr. Sung: Absolutely. So when we originally conceived the program, we focused on patients who lived within an hour of our transplant center. And in part, that was because, as you know, unfortunately, things can sometimes go wrong during transplant. One of the most concerning ones is infections. And if a patient were to develop a neutropenic fever, we would want them to be seen as urgently as possible within an hour. And that’s where our limitation comes from.

So for our patients who live more than an hour away, those are the ones that we will have relocate to temporary lodging near our transplant center. And we’ve worked with several facilities in the area that have clean, furnished units that are available for rent. Many insurances also include lodging benefits for patients during stem cell transplant, recognizing this need. And historically, those [patients] were not considered part of our transplant patient cohorts.

I have not mentioned, but we initially did this in a phase 1 study, and we’re now studying it in a series of randomized, phase 2 studies that I can go into detail later on. And because they were not necessarily in their home, but a temporary lodging environment, those patients who relocated to Durham were not eligible for a home transplant study.

However, in the setting of the COVID-19 pandemic, we’ve actually pivoted our program in many ways. Specifically, if you think about a patient who’s coming into contact with the medical system, they come to the hospital, they meet someone at the door who is screening them for COVID-19. They see someone who checks them in at the front desk. A medical assistant takes them in the back. Someone calls their labs and phlebotomy. They may encounter other patients and environmental services, other individuals in the setting. You’re talking about dozens of different encounters. Who knows how many surfaces that potentially someone with COVID-19 has coughed on or contaminated?

And in contrast, you have house calls, which even if they are located in the temporary lodging, that’s just one or two individuals going into their living environment. They’re not encountering any different surfaces. And so, in the setting of COVID-19, we felt that this platform had the potential to help protect all our transplant patients who are among the most vulnerable patients, the most immunocompromised patients, and so we expanded our program to include those individuals as well.
 

Dr. Henry: So ... what are the actual outcomes of your patients in terms of how they’re doing, engrafting, and getting cured of their malignancy?

Dr. Sung: So as I mentioned, we first did this in a phase 1 safety and feasibility pilot study of both autologous and allo-transplant patients. This was presented at the annual meeting of the American Society of Hematology [Blood. 2017;130:745]. And we’re actually about ready to submit our manuscript on this.

And we found no difference in outcomes between patients who received care in the home transplant setting versus those who received conventional care either in the day hospital or hospital environment. The process appeared safe. Patients did just as well, if not better. Certainly, anecdotally, patients would talk about feeling so much more comfortable and happier being cared for in that home environment.

And we are now in the process of formally studying these outcomes in two NIH [National Institutes of Health]-funded clinical trials, one focused on allogeneic transplant patients [NCT02218151] and the other focused on autologous transplant patients [NCT01725022].
 

Dr. Henry: So of course, I’m waiting for this next question, which is cost. The services are the same, but you have people traveling, people who are highly skilled caregivers. Have you looked at cost differences from hospital versus home?

Dr. Sung: Absolutely. So you do have increased upfront costs because you have travel time for advanced practice providers and nurses. Not only that, but when a nurse is helping to give a patient a blood transfusion in the home environment, they’re 1:1 with that patient as opposed to the day hospital where a nurse could help with transfusions simultaneously for multiple patients. At the same time, by keeping patients out of the hospital, you have drastic, significant cost savings in that way.

In addition, I should mention, part of why we’re conducting these randomized, phase 2 clinical trials is we believe home care actually has the potential to decrease complications. One area of my research is on the impact of the microbiome, the bacteria in the gut, on transplant outcomes. And we’ve done a number of studies, many in collaboration with Memorial Sloan Kettering, showing that disruption of the microbiota, the bacteria in the gut, is associated with increased infections, graft-versus-host disease, and treatment-related mortality if we’re able to keep patients in their home setting.

However, I actually should go back a step. It’s well known that, if you take an individual from their home setting and put them in a foreign environment such as the hospital, that new environment, that new diet, hospital food as opposed to home food, and so forth, can dramatically shift the microbiome. Our hypothesis is that, by keeping patients in the home environment, their familiar environment will be able to help preserve their microbiome, thus decreasing infections, graft-versus-host disease, and other complications. That’s actually the goal of our studies: to see if we can preserve the microbiome and decrease complications.
 

Dr. Henry: So how will you evaluate that? Are you doing fecal studies, patient culture studies? How are you testing that?

Dr. Sung: So we have a very broad biobank program where we collect stool on our transplantations, pretransplant, day 0, weekly for the first month. And then, in the case of our allogeneic transplant patients, day 60, 90, 180, and 365.

And we do that both in our home transplant patients as well as their matched controls on the phase 2 studies. And we also collect it on a lot of our other transplant patients as part of our biobanking programs and our observational studies to try to understand what’s going on during transplant and how to help improve transplant outcomes.
 

Dr. Henry: Do you have any results of that? You’re probably showing a difference.

Dr. Sung: We think so, on some preliminary results, but those were based on small numbers of patients. And we’re really hoping that these randomized clinical trials with the larger numbers of patients enrolled will help show that difference.

But getting back to your earlier question about cost, a case of graft-versus-host disease, grade 2 or higher, can add about $100,000 to the cost of care. So if you prevent one case of bad gut or liver graft-versus-host disease, those are your cost savings right there.

The randomized, phase 2 trial for allogeneic transplant patients, the primary endpoint is graft-versus-host disease. So we’re looking at the microbiome and those associations and the prevention of GVHD. For the randomized clinical trial in autologous transplant patients – with autologous stem cells, you’re not going to get GVHD – but we do hope to improve quality of life and long-term outcomes in those patients as well.
 

Dr. Henry: Wonderful. Well, Tony, I really want to thank you so much for talking with us today.

Dr. Sung: Thank you very much for this opportunity. And again, I also want to just thank everyone who’s been involved in these studies, the advanced practice providers and nurses who are caring for our patients at home, the study staff who have been involved. Particularly, I’d like to highlight the role of both Nelson Chao, who’s our division chief and my mentor who piloted and first developed home transplant, and Kristin Nichols, our research nurse who has really led the drive forward.

Dr. Sung and Dr. Henry have no relevant disclosures. The trials are funded by grants from the National Institutes of Health.