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Efficacy and safety profiles were similar for subcutaneous and standard IV rituximab when given as first-line therapy to adults with follicular lymphoma, based on results of a phase III clinical trial published online in Lancet Haematology.

Administering rituximab by IV infusion can take up to 6 hours to complete and requires continuous monitoring. Subcutaneous delivery takes approximately 6 minutes using a new rituximab formulation that is 12 times more concentrated to reduce the administered volume. The new formulation is expected to reduce the burden of treatment for patients, as well as for the health care system, said Andrew Davies, PhD, of the Cancer Research UK Centre, Southampton, and his associates.

They compared the two agents in an international open-label trial funded by Hoffmann-La Roche, maker of the subcutaneous formulation. Adult patients at 113 medical centers in 30 countries were randomly assigned to receive either IV (205 patients) or subcutaneous (205 patients) rituximab during induction therapy with six to eight cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CVP (cyclophosphamide, vincristine, and prednisone). They continued with rituximab as maintenance therapy every 2 months for 2 years. The median duration of treatment was 27 months, and median follow-up was 37 months.

The primary efficacy end point – overall (complete or partial) response rate at the end of induction, based on investigator assessment confirmed by an independent review panel of radiologists – was 84.9% with IV and 84.4% with subcutaneous rituximab, a nonsignificant difference. Similarly, the overall response rate at the end of maintenance therapy was not significantly different between the two groups, at 78.1% and 77.9%, respectively.

Progression-free survival (hazard ratio, 0.84) and event-free survival (HR, 0.91) also did not differ significantly between the two study groups, the investigators said (Lancet Haematol. 2017 doi: 10.1016/S2352.3026(17)30078-9).

The rates of adverse events, grade 3 or higher adverse events, and serious adverse events also were similar for IV and subcutaneous formulations of rituximab. “Administration-related reactions were more common in the subcutaneous group but were predominantly mild-to-moderate local injection-site reactions, such as mild pain, swelling and erythema, reflecting the expected change in safety profile when switching to the subcutaneous route of administration,” Dr. Davies and his associates said.

These results indicate that subcutaneous administration of rituximab along with chemotherapy doesn’t compromise the agent’s antilymphoma activity, they added.

Efficacy and safety profiles were similar for subcutaneous and standard IV rituximab when given as first-line therapy to adults with follicular lymphoma, based on results of a phase III clinical trial published online in Lancet Haematology.

Administering rituximab by IV infusion can take up to 6 hours to complete and requires continuous monitoring. Subcutaneous delivery takes approximately 6 minutes using a new rituximab formulation that is 12 times more concentrated to reduce the administered volume. The new formulation is expected to reduce the burden of treatment for patients, as well as for the health care system, said Andrew Davies, PhD, of the Cancer Research UK Centre, Southampton, and his associates.

They compared the two agents in an international open-label trial funded by Hoffmann-La Roche, maker of the subcutaneous formulation. Adult patients at 113 medical centers in 30 countries were randomly assigned to receive either IV (205 patients) or subcutaneous (205 patients) rituximab during induction therapy with six to eight cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CVP (cyclophosphamide, vincristine, and prednisone). They continued with rituximab as maintenance therapy every 2 months for 2 years. The median duration of treatment was 27 months, and median follow-up was 37 months.

The primary efficacy end point – overall (complete or partial) response rate at the end of induction, based on investigator assessment confirmed by an independent review panel of radiologists – was 84.9% with IV and 84.4% with subcutaneous rituximab, a nonsignificant difference. Similarly, the overall response rate at the end of maintenance therapy was not significantly different between the two groups, at 78.1% and 77.9%, respectively.

Progression-free survival (hazard ratio, 0.84) and event-free survival (HR, 0.91) also did not differ significantly between the two study groups, the investigators said (Lancet Haematol. 2017 doi: 10.1016/S2352.3026(17)30078-9).

The rates of adverse events, grade 3 or higher adverse events, and serious adverse events also were similar for IV and subcutaneous formulations of rituximab. “Administration-related reactions were more common in the subcutaneous group but were predominantly mild-to-moderate local injection-site reactions, such as mild pain, swelling and erythema, reflecting the expected change in safety profile when switching to the subcutaneous route of administration,” Dr. Davies and his associates said.

These results indicate that subcutaneous administration of rituximab along with chemotherapy doesn’t compromise the agent’s antilymphoma activity, they added.

Efficacy and safety profiles were similar for subcutaneous and standard IV rituximab when given as first-line therapy to adults with follicular lymphoma, based on results of a phase III clinical trial published online in Lancet Haematology.

Administering rituximab by IV infusion can take up to 6 hours to complete and requires continuous monitoring. Subcutaneous delivery takes approximately 6 minutes using a new rituximab formulation that is 12 times more concentrated to reduce the administered volume. The new formulation is expected to reduce the burden of treatment for patients, as well as for the health care system, said Andrew Davies, PhD, of the Cancer Research UK Centre, Southampton, and his associates.

They compared the two agents in an international open-label trial funded by Hoffmann-La Roche, maker of the subcutaneous formulation. Adult patients at 113 medical centers in 30 countries were randomly assigned to receive either IV (205 patients) or subcutaneous (205 patients) rituximab during induction therapy with six to eight cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CVP (cyclophosphamide, vincristine, and prednisone). They continued with rituximab as maintenance therapy every 2 months for 2 years. The median duration of treatment was 27 months, and median follow-up was 37 months.

The primary efficacy end point – overall (complete or partial) response rate at the end of induction, based on investigator assessment confirmed by an independent review panel of radiologists – was 84.9% with IV and 84.4% with subcutaneous rituximab, a nonsignificant difference. Similarly, the overall response rate at the end of maintenance therapy was not significantly different between the two groups, at 78.1% and 77.9%, respectively.

Progression-free survival (hazard ratio, 0.84) and event-free survival (HR, 0.91) also did not differ significantly between the two study groups, the investigators said (Lancet Haematol. 2017 doi: 10.1016/S2352.3026(17)30078-9).

The rates of adverse events, grade 3 or higher adverse events, and serious adverse events also were similar for IV and subcutaneous formulations of rituximab. “Administration-related reactions were more common in the subcutaneous group but were predominantly mild-to-moderate local injection-site reactions, such as mild pain, swelling and erythema, reflecting the expected change in safety profile when switching to the subcutaneous route of administration,” Dr. Davies and his associates said.

These results indicate that subcutaneous administration of rituximab along with chemotherapy doesn’t compromise the agent’s antilymphoma activity, they added.

Prescription-drug monitoring programs (PDMPs), which require physicians to check drug registries before writing prescriptions, dramatically cut the odds of doctor shopping for opioid pain relievers, according to researchers from the Substance Abuse and Mental Health Services Administration (SAMHSA).

The PDMPs are electronic databases that track prescribing of controlled substances and identify people at high risk of misusing the drugs. The researchers analyzed annual nationwide surveys of drug use and health from 2004 to 2014, when 36 states implemented PDMPs. Their paper is the first to examine the role of PDMPs on individual-level opioid-related outcomes.

Every state except Missouri now has a PDMP. In some states it is mandatory to have a PDMP, but in some states it is voluntarily implemented. In states with mandatory checking, the odds that ≥ 2 doctors would be giving pain relievers for nonmedical purposes to a single patient were reduced by 80%. In states with voluntary monitoring, the odds dropped by 56%.

PDMPs also were associated with 10 to 20 fewer days of use of painkillers for nonmedical purposes in the previous year.

Prescription-drug monitoring programs (PDMPs), which require physicians to check drug registries before writing prescriptions, dramatically cut the odds of doctor shopping for opioid pain relievers, according to researchers from the Substance Abuse and Mental Health Services Administration (SAMHSA).

The PDMPs are electronic databases that track prescribing of controlled substances and identify people at high risk of misusing the drugs. The researchers analyzed annual nationwide surveys of drug use and health from 2004 to 2014, when 36 states implemented PDMPs. Their paper is the first to examine the role of PDMPs on individual-level opioid-related outcomes.

Every state except Missouri now has a PDMP. In some states it is mandatory to have a PDMP, but in some states it is voluntarily implemented. In states with mandatory checking, the odds that ≥ 2 doctors would be giving pain relievers for nonmedical purposes to a single patient were reduced by 80%. In states with voluntary monitoring, the odds dropped by 56%.

PDMPs also were associated with 10 to 20 fewer days of use of painkillers for nonmedical purposes in the previous year.

Prescription-drug monitoring programs (PDMPs), which require physicians to check drug registries before writing prescriptions, dramatically cut the odds of doctor shopping for opioid pain relievers, according to researchers from the Substance Abuse and Mental Health Services Administration (SAMHSA).

The PDMPs are electronic databases that track prescribing of controlled substances and identify people at high risk of misusing the drugs. The researchers analyzed annual nationwide surveys of drug use and health from 2004 to 2014, when 36 states implemented PDMPs. Their paper is the first to examine the role of PDMPs on individual-level opioid-related outcomes.

Every state except Missouri now has a PDMP. In some states it is mandatory to have a PDMP, but in some states it is voluntarily implemented. In states with mandatory checking, the odds that ≥ 2 doctors would be giving pain relievers for nonmedical purposes to a single patient were reduced by 80%. In states with voluntary monitoring, the odds dropped by 56%.

PDMPs also were associated with 10 to 20 fewer days of use of painkillers for nonmedical purposes in the previous year.

In 2015, nearly 2.4 million Americans had an opioid use disorder. Close to 80% did not receive treatment. To help change those numbers, the Substance Abuse and Mental Health Services Administration (SAMHSA) has developed a free mobile application called MATx that supports medication-assisted treatment. The app “empowers health care practitioners to provide effective, evidence-based care for people with opioid use disorder.” Features include the following:

• Information on treatment approaches and medications approved by the FDA for use in treating opioid use disorders;
• A buprenorphine prescribing guide, including information on the Drug Addiction Treatment Act of 2000 waiver process and patient limits;
• Clinical support tools, such as treatment guidelines, ICD-10 coding, and recommendations for working with special populations;
• Access to critical helplines and SAMHSA’s treatment locators.

For more information on the app, visit http://store.samhsa.gov/apps/mat/tools/index.html?WT.ac=PEPAdSpreadWord20161018Prof.

In 2015, nearly 2.4 million Americans had an opioid use disorder. Close to 80% did not receive treatment. To help change those numbers, the Substance Abuse and Mental Health Services Administration (SAMHSA) has developed a free mobile application called MATx that supports medication-assisted treatment. The app “empowers health care practitioners to provide effective, evidence-based care for people with opioid use disorder.” Features include the following:

• Information on treatment approaches and medications approved by the FDA for use in treating opioid use disorders;
• A buprenorphine prescribing guide, including information on the Drug Addiction Treatment Act of 2000 waiver process and patient limits;
• Clinical support tools, such as treatment guidelines, ICD-10 coding, and recommendations for working with special populations;
• Access to critical helplines and SAMHSA’s treatment locators.

For more information on the app, visit http://store.samhsa.gov/apps/mat/tools/index.html?WT.ac=PEPAdSpreadWord20161018Prof.

In 2015, nearly 2.4 million Americans had an opioid use disorder. Close to 80% did not receive treatment. To help change those numbers, the Substance Abuse and Mental Health Services Administration (SAMHSA) has developed a free mobile application called MATx that supports medication-assisted treatment. The app “empowers health care practitioners to provide effective, evidence-based care for people with opioid use disorder.” Features include the following:

• Information on treatment approaches and medications approved by the FDA for use in treating opioid use disorders;
• A buprenorphine prescribing guide, including information on the Drug Addiction Treatment Act of 2000 waiver process and patient limits;
• Clinical support tools, such as treatment guidelines, ICD-10 coding, and recommendations for working with special populations;
• Access to critical helplines and SAMHSA’s treatment locators.

For more information on the app, visit http://store.samhsa.gov/apps/mat/tools/index.html?WT.ac=PEPAdSpreadWord20161018Prof.

MONTREAL – A combination of placenta-derived stem cells and umbilical cord blood was associated with early engraftment and high degrees of cord blood donor chimerism in the treatment of children with both malignant and nonmalignant hematologic conditions requiring stem cell transplantation, updated results of a pilot study show.

Among 16 children treated with the combination, the probability of neutrophil engraftment was 87.5%, and all patients who had neutrophil engraftment went on to have platelet engraftment. The probability of 12-month overall survival was 81.2%, reported Allyson Flower, MD, from Boston Children’s Health Physicians in Hawthorne, N.Y. “The probability of grade II-IV acute graft vs. host disease was 12.5%, compared with 32.5% seen with unrelated cord blood in our group’s previous studies. Cellular immune reconstitution was robust,” she said at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Augmenting cord blood

Although unrelated donor cord blood transplantation expands the donor pool, is rapidly available, and is associated with decreases in both severe acute graft vs. host disease (GVHD) and chronic GVHD, compared with other stem cell sources, the technique is hampered by limited cell doses, prolonged immune reconstitution time, delays in hematopoietic recovery, and a higher incidence of graft failure.

Early studies of myeloablative conditioning followed by unrelated umbilical or placental blood transplantation showed a median of 22-24 days to neutrophil engraftment (Blood 1996 88:795-802; N Engl J Med. 1996;335:157-66), Dr. Flower noted.

More recently, a multivariate analysis of patients who underwent reduced-intensity conditioning followed by hematopoietic stem cell transplant with unrelated cord blood showed that graft failure was an independent risk factor for worse overall survival (Biol Blood Marrow Transplant. 2013 Apr;19:4;552-61).

Multiple groups have shown that adding human placenta–derived stem cells (HPDSC) to cord blood transplantation can facilitate more rapid hematopoietic engraftment by increasing the number of stem cells, increasing the proportion of hematopoietic progenitor cells, and providing additional, immature CD34+/CD45– progenitor cells.

In a single-arm, nonrandomized study, the investigators enrolled 16 patients ranging in age from 0.3 to 15.7 years with inborn errors of metabolism, marrow failure syndromes, severe immunodeficiency states, or hematologic malignancies.

Malignant conditions included B-cell precursor acute lymphoblastic leukemia (B-ALL; four patients), acute myeloid leukemia (AML; two), and T-cell ALL (one) in first complete remission, and T-cell lymphoblastic lymphoma following induction failure (one). Nonmalignant conditions included adrenoleukodystrophy (two patients), amegakaryotic thrombocytopenia (one), severe combined immunodeficiency (SCID; two), dyskeratosis congenita (one), chronic granulomatous disease (one), and severe congenital neutropenia (one).

The patients first underwent either myeloablative or reduced-intensity conditioning, followed 10 days later by infusion of unrelated cord blood and HPDSCs. Prior to HPDSC infusion, patients were medicated with diphenhydramine and hydrocortisone to prevent or reduce potential sensitivity reactions. HPDSCs were infused no sooner than 4 hours after the end of the cord blood infusion.

Patients received GVHD prophylaxis with either tacrolimus or cyclosporine, plus mycophenolate mofetil.

The combination appeared to be safe, with no cases of grade 3 or 4 toxicity secondary to HPDSC infusion.

The probability of neutrophil engraftment was 87.5%, with engraftment occurring at a median of 23 days (range 13-53). As noted before, all patients who had neutrophil engraftment had platelet engraftment, which was achieved at a median of 47 days (range, 20-98). In the group’s previous studies, median time to platelet engraftment was 53 days for patients who had undergone reduced-intensity conditioning, and 118 days for patients who had undergone myeloablation.

The probability of grade 2-4 acute GVHD within 100 days was 12.5%, and there were no cases of chronic GVHD.

Respective percentages of cord blood donor chimerism at days 30, 60, 100, and 180 were 88%, 98%, 99%, and 99%.

Immune reconstitution was strong, with normalization of mean CD3+, CD19+, and CD56+ cells occurring by day 100, CD8+ cells by day 180, and CD4+ cells by day 270.

There were three patient deaths: one from adenoviremia in a patient with B-ALL and CNS relapse, who had neutrophil engraftment at day 21; one in a patient with SCID, from adenoviremia and multiple system organ failure, who did not have engraftment before death; and one in a patient with severe congenital neutrophilia, who also did not have neutrophil engraftment.

None of the eight patients with malignant disease have experienced relapse to date, Dr. Flower noted.

The study was funded by a grant from Celgene Cellular Therapeutics. Dr. Flower reported having no conflicts of interest.

hematologynews@frontlinemedcom.com

MONTREAL – A combination of placenta-derived stem cells and umbilical cord blood was associated with early engraftment and high degrees of cord blood donor chimerism in the treatment of children with both malignant and nonmalignant hematologic conditions requiring stem cell transplantation, updated results of a pilot study show.

Among 16 children treated with the combination, the probability of neutrophil engraftment was 87.5%, and all patients who had neutrophil engraftment went on to have platelet engraftment. The probability of 12-month overall survival was 81.2%, reported Allyson Flower, MD, from Boston Children’s Health Physicians in Hawthorne, N.Y. “The probability of grade II-IV acute graft vs. host disease was 12.5%, compared with 32.5% seen with unrelated cord blood in our group’s previous studies. Cellular immune reconstitution was robust,” she said at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Augmenting cord blood

Although unrelated donor cord blood transplantation expands the donor pool, is rapidly available, and is associated with decreases in both severe acute graft vs. host disease (GVHD) and chronic GVHD, compared with other stem cell sources, the technique is hampered by limited cell doses, prolonged immune reconstitution time, delays in hematopoietic recovery, and a higher incidence of graft failure.

Early studies of myeloablative conditioning followed by unrelated umbilical or placental blood transplantation showed a median of 22-24 days to neutrophil engraftment (Blood 1996 88:795-802; N Engl J Med. 1996;335:157-66), Dr. Flower noted.

More recently, a multivariate analysis of patients who underwent reduced-intensity conditioning followed by hematopoietic stem cell transplant with unrelated cord blood showed that graft failure was an independent risk factor for worse overall survival (Biol Blood Marrow Transplant. 2013 Apr;19:4;552-61).

Multiple groups have shown that adding human placenta–derived stem cells (HPDSC) to cord blood transplantation can facilitate more rapid hematopoietic engraftment by increasing the number of stem cells, increasing the proportion of hematopoietic progenitor cells, and providing additional, immature CD34+/CD45– progenitor cells.

In a single-arm, nonrandomized study, the investigators enrolled 16 patients ranging in age from 0.3 to 15.7 years with inborn errors of metabolism, marrow failure syndromes, severe immunodeficiency states, or hematologic malignancies.

Malignant conditions included B-cell precursor acute lymphoblastic leukemia (B-ALL; four patients), acute myeloid leukemia (AML; two), and T-cell ALL (one) in first complete remission, and T-cell lymphoblastic lymphoma following induction failure (one). Nonmalignant conditions included adrenoleukodystrophy (two patients), amegakaryotic thrombocytopenia (one), severe combined immunodeficiency (SCID; two), dyskeratosis congenita (one), chronic granulomatous disease (one), and severe congenital neutropenia (one).

The patients first underwent either myeloablative or reduced-intensity conditioning, followed 10 days later by infusion of unrelated cord blood and HPDSCs. Prior to HPDSC infusion, patients were medicated with diphenhydramine and hydrocortisone to prevent or reduce potential sensitivity reactions. HPDSCs were infused no sooner than 4 hours after the end of the cord blood infusion.

Patients received GVHD prophylaxis with either tacrolimus or cyclosporine, plus mycophenolate mofetil.

The combination appeared to be safe, with no cases of grade 3 or 4 toxicity secondary to HPDSC infusion.

The probability of neutrophil engraftment was 87.5%, with engraftment occurring at a median of 23 days (range 13-53). As noted before, all patients who had neutrophil engraftment had platelet engraftment, which was achieved at a median of 47 days (range, 20-98). In the group’s previous studies, median time to platelet engraftment was 53 days for patients who had undergone reduced-intensity conditioning, and 118 days for patients who had undergone myeloablation.

The probability of grade 2-4 acute GVHD within 100 days was 12.5%, and there were no cases of chronic GVHD.

Respective percentages of cord blood donor chimerism at days 30, 60, 100, and 180 were 88%, 98%, 99%, and 99%.

Immune reconstitution was strong, with normalization of mean CD3+, CD19+, and CD56+ cells occurring by day 100, CD8+ cells by day 180, and CD4+ cells by day 270.

There were three patient deaths: one from adenoviremia in a patient with B-ALL and CNS relapse, who had neutrophil engraftment at day 21; one in a patient with SCID, from adenoviremia and multiple system organ failure, who did not have engraftment before death; and one in a patient with severe congenital neutrophilia, who also did not have neutrophil engraftment.

None of the eight patients with malignant disease have experienced relapse to date, Dr. Flower noted.

The study was funded by a grant from Celgene Cellular Therapeutics. Dr. Flower reported having no conflicts of interest.

hematologynews@frontlinemedcom.com

MONTREAL – A combination of placenta-derived stem cells and umbilical cord blood was associated with early engraftment and high degrees of cord blood donor chimerism in the treatment of children with both malignant and nonmalignant hematologic conditions requiring stem cell transplantation, updated results of a pilot study show.

Among 16 children treated with the combination, the probability of neutrophil engraftment was 87.5%, and all patients who had neutrophil engraftment went on to have platelet engraftment. The probability of 12-month overall survival was 81.2%, reported Allyson Flower, MD, from Boston Children’s Health Physicians in Hawthorne, N.Y. “The probability of grade II-IV acute graft vs. host disease was 12.5%, compared with 32.5% seen with unrelated cord blood in our group’s previous studies. Cellular immune reconstitution was robust,” she said at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Augmenting cord blood

Although unrelated donor cord blood transplantation expands the donor pool, is rapidly available, and is associated with decreases in both severe acute graft vs. host disease (GVHD) and chronic GVHD, compared with other stem cell sources, the technique is hampered by limited cell doses, prolonged immune reconstitution time, delays in hematopoietic recovery, and a higher incidence of graft failure.

Early studies of myeloablative conditioning followed by unrelated umbilical or placental blood transplantation showed a median of 22-24 days to neutrophil engraftment (Blood 1996 88:795-802; N Engl J Med. 1996;335:157-66), Dr. Flower noted.

More recently, a multivariate analysis of patients who underwent reduced-intensity conditioning followed by hematopoietic stem cell transplant with unrelated cord blood showed that graft failure was an independent risk factor for worse overall survival (Biol Blood Marrow Transplant. 2013 Apr;19:4;552-61).

Multiple groups have shown that adding human placenta–derived stem cells (HPDSC) to cord blood transplantation can facilitate more rapid hematopoietic engraftment by increasing the number of stem cells, increasing the proportion of hematopoietic progenitor cells, and providing additional, immature CD34+/CD45– progenitor cells.

In a single-arm, nonrandomized study, the investigators enrolled 16 patients ranging in age from 0.3 to 15.7 years with inborn errors of metabolism, marrow failure syndromes, severe immunodeficiency states, or hematologic malignancies.

Malignant conditions included B-cell precursor acute lymphoblastic leukemia (B-ALL; four patients), acute myeloid leukemia (AML; two), and T-cell ALL (one) in first complete remission, and T-cell lymphoblastic lymphoma following induction failure (one). Nonmalignant conditions included adrenoleukodystrophy (two patients), amegakaryotic thrombocytopenia (one), severe combined immunodeficiency (SCID; two), dyskeratosis congenita (one), chronic granulomatous disease (one), and severe congenital neutropenia (one).

The patients first underwent either myeloablative or reduced-intensity conditioning, followed 10 days later by infusion of unrelated cord blood and HPDSCs. Prior to HPDSC infusion, patients were medicated with diphenhydramine and hydrocortisone to prevent or reduce potential sensitivity reactions. HPDSCs were infused no sooner than 4 hours after the end of the cord blood infusion.

Patients received GVHD prophylaxis with either tacrolimus or cyclosporine, plus mycophenolate mofetil.

The combination appeared to be safe, with no cases of grade 3 or 4 toxicity secondary to HPDSC infusion.

The probability of neutrophil engraftment was 87.5%, with engraftment occurring at a median of 23 days (range 13-53). As noted before, all patients who had neutrophil engraftment had platelet engraftment, which was achieved at a median of 47 days (range, 20-98). In the group’s previous studies, median time to platelet engraftment was 53 days for patients who had undergone reduced-intensity conditioning, and 118 days for patients who had undergone myeloablation.

The probability of grade 2-4 acute GVHD within 100 days was 12.5%, and there were no cases of chronic GVHD.

Respective percentages of cord blood donor chimerism at days 30, 60, 100, and 180 were 88%, 98%, 99%, and 99%.

Immune reconstitution was strong, with normalization of mean CD3+, CD19+, and CD56+ cells occurring by day 100, CD8+ cells by day 180, and CD4+ cells by day 270.

There were three patient deaths: one from adenoviremia in a patient with B-ALL and CNS relapse, who had neutrophil engraftment at day 21; one in a patient with SCID, from adenoviremia and multiple system organ failure, who did not have engraftment before death; and one in a patient with severe congenital neutrophilia, who also did not have neutrophil engraftment.

None of the eight patients with malignant disease have experienced relapse to date, Dr. Flower noted.

The study was funded by a grant from Celgene Cellular Therapeutics. Dr. Flower reported having no conflicts of interest.

hematologynews@frontlinemedcom.com

The National Institute of Occupational Safety and Health (NIOSH) released 2 new modules for tracking sharps incidents, blood, and body fluid exposures. The Occupational Health Safety Network (OHSN), a free, voluntary system “uniquely available” to U.S. health care facilities, collects injury, data such as date of injury or illness, location of incident, description of illness, and days away from work. The information is intended to help facilities identify high-risk jobs, develop interventions for safety and health of hospital staff, and objectively measure impact over time.

The modules join others that track incidence of slips, trips, and falls; patient handling injuries; and workplace violence.

The OHSN developers say that the secure electronic system hosts facilities across 20 states, all providing data to the web-based portal. The system allows participants to determine the root cause for each incident, analyzes the data, and presents the results in easy-to-read charts. Members can use OHSN to analyze and report workplace-specific data to illustrate the magnitude of injury and illness events among workers, monitor trends, and access a library of resources specific to health care.

As the pool of participants expands, “an increasingly more accurate picture can be drawn,” NIOSH says, and recommendations, interventions, and prevention strategies utilized.

To enroll, visit https://www.cdc.gov/niosh/topics/ohsn/enrollment.html?s_cid=3ni7d2niupdateOHSN-Enroll032017.

The National Institute of Occupational Safety and Health (NIOSH) released 2 new modules for tracking sharps incidents, blood, and body fluid exposures. The Occupational Health Safety Network (OHSN), a free, voluntary system “uniquely available” to U.S. health care facilities, collects injury, data such as date of injury or illness, location of incident, description of illness, and days away from work. The information is intended to help facilities identify high-risk jobs, develop interventions for safety and health of hospital staff, and objectively measure impact over time.

The modules join others that track incidence of slips, trips, and falls; patient handling injuries; and workplace violence.

The OHSN developers say that the secure electronic system hosts facilities across 20 states, all providing data to the web-based portal. The system allows participants to determine the root cause for each incident, analyzes the data, and presents the results in easy-to-read charts. Members can use OHSN to analyze and report workplace-specific data to illustrate the magnitude of injury and illness events among workers, monitor trends, and access a library of resources specific to health care.

As the pool of participants expands, “an increasingly more accurate picture can be drawn,” NIOSH says, and recommendations, interventions, and prevention strategies utilized.

To enroll, visit https://www.cdc.gov/niosh/topics/ohsn/enrollment.html?s_cid=3ni7d2niupdateOHSN-Enroll032017.

The National Institute of Occupational Safety and Health (NIOSH) released 2 new modules for tracking sharps incidents, blood, and body fluid exposures. The Occupational Health Safety Network (OHSN), a free, voluntary system “uniquely available” to U.S. health care facilities, collects injury, data such as date of injury or illness, location of incident, description of illness, and days away from work. The information is intended to help facilities identify high-risk jobs, develop interventions for safety and health of hospital staff, and objectively measure impact over time.

The modules join others that track incidence of slips, trips, and falls; patient handling injuries; and workplace violence.

The OHSN developers say that the secure electronic system hosts facilities across 20 states, all providing data to the web-based portal. The system allows participants to determine the root cause for each incident, analyzes the data, and presents the results in easy-to-read charts. Members can use OHSN to analyze and report workplace-specific data to illustrate the magnitude of injury and illness events among workers, monitor trends, and access a library of resources specific to health care.

As the pool of participants expands, “an increasingly more accurate picture can be drawn,” NIOSH says, and recommendations, interventions, and prevention strategies utilized.

To enroll, visit https://www.cdc.gov/niosh/topics/ohsn/enrollment.html?s_cid=3ni7d2niupdateOHSN-Enroll032017.

Ibrutinib is active in patients with previously treated marginal zone lymphoma (MZL) and has a good safety profile, the results of a multicenter, open-label phase II trial published in Blood suggest.

Nearly half of 63 patients responded to monotherapy with the once-daily oral inhibitor of Bruton tyrosine kinase, and ibrutinib was generally well tolerated, according to the study (Blood. 2017;129:2224-32). The results prompted the U.S. Food and Drug Administration to grant accelerated approval of ibrutinib for patients with MZL who were previously treated with at least one prior anti-CD20–based therapy.

“MZL is frequently linked to chronic infection, which may induce B-cell receptor (BCR) signaling, resulting in aberrant B-cell survival and proliferation,” note the investigators, who were led by Ariela Noy, MD, a hematologic oncologist with the Lymphoma Service at the Memorial Sloan-Kettering Cancer Center, New York. “Single-agent ibrutinib induced durable responses with a favorable benefit–risk profile in patients with previously treated MZL, confirming the role of BCR signaling in this malignancy.”

“As the only approved therapy, ibrutinib provides a treatment option without chemotherapy for MZL,” they maintain. “Future studies will investigate ibrutinib in treatment-naive patients or as combination strategies in relapsed/refractory MZL.”

In the trial, which was funded by Pharmacyclics, an AbbVie Company, patients with MZL of all subtypes who had received at least one prior therapy with an anti-CD20 antibody–containing regimen were treated with 560 mg ibrutinib (Imbruvica) orally once daily. The median number of prior systemic therapies was two, and 63% had received prior chemoimmunotherapy.

The overall response rate, as assessed by an independent review committee using 2007 International Working Group criteria – the trial’s primary endpoint – was 48%, according to the published results. Benefit was similar across patients who differed regarding MZL subtype, number of prior regimen, and previous receipt of chemoimmunotherapy

After a 19.4-month median follow-up, the median duration of response was not reached, and median progression-free survival was 14.2 months.

The most common grade 3 or worse adverse events were anemia (14%), pneumonia (8%), and fatigue (6%). Serious adverse events of any grade affected 44% of patients. The most common was grade 3 or 4 pneumonia. Adverse events led to treatment discontinuation in 17% of patients and dose reductions in 10%.

“Due to evidence of pseudoprogression in our trial … biopsies may be warranted to differentiate between true lymphoma progression and immune-mediated antitumor response,” the investigators note.

Dr. Noy disclosed that she has received research funding from Pharmacyclics.

hematologynews@frontlinemedcom.com

Ibrutinib is active in patients with previously treated marginal zone lymphoma (MZL) and has a good safety profile, the results of a multicenter, open-label phase II trial published in Blood suggest.

Nearly half of 63 patients responded to monotherapy with the once-daily oral inhibitor of Bruton tyrosine kinase, and ibrutinib was generally well tolerated, according to the study (Blood. 2017;129:2224-32). The results prompted the U.S. Food and Drug Administration to grant accelerated approval of ibrutinib for patients with MZL who were previously treated with at least one prior anti-CD20–based therapy.

“MZL is frequently linked to chronic infection, which may induce B-cell receptor (BCR) signaling, resulting in aberrant B-cell survival and proliferation,” note the investigators, who were led by Ariela Noy, MD, a hematologic oncologist with the Lymphoma Service at the Memorial Sloan-Kettering Cancer Center, New York. “Single-agent ibrutinib induced durable responses with a favorable benefit–risk profile in patients with previously treated MZL, confirming the role of BCR signaling in this malignancy.”

“As the only approved therapy, ibrutinib provides a treatment option without chemotherapy for MZL,” they maintain. “Future studies will investigate ibrutinib in treatment-naive patients or as combination strategies in relapsed/refractory MZL.”

In the trial, which was funded by Pharmacyclics, an AbbVie Company, patients with MZL of all subtypes who had received at least one prior therapy with an anti-CD20 antibody–containing regimen were treated with 560 mg ibrutinib (Imbruvica) orally once daily. The median number of prior systemic therapies was two, and 63% had received prior chemoimmunotherapy.

The overall response rate, as assessed by an independent review committee using 2007 International Working Group criteria – the trial’s primary endpoint – was 48%, according to the published results. Benefit was similar across patients who differed regarding MZL subtype, number of prior regimen, and previous receipt of chemoimmunotherapy

After a 19.4-month median follow-up, the median duration of response was not reached, and median progression-free survival was 14.2 months.

The most common grade 3 or worse adverse events were anemia (14%), pneumonia (8%), and fatigue (6%). Serious adverse events of any grade affected 44% of patients. The most common was grade 3 or 4 pneumonia. Adverse events led to treatment discontinuation in 17% of patients and dose reductions in 10%.

“Due to evidence of pseudoprogression in our trial … biopsies may be warranted to differentiate between true lymphoma progression and immune-mediated antitumor response,” the investigators note.

Dr. Noy disclosed that she has received research funding from Pharmacyclics.

hematologynews@frontlinemedcom.com

Ibrutinib is active in patients with previously treated marginal zone lymphoma (MZL) and has a good safety profile, the results of a multicenter, open-label phase II trial published in Blood suggest.

Nearly half of 63 patients responded to monotherapy with the once-daily oral inhibitor of Bruton tyrosine kinase, and ibrutinib was generally well tolerated, according to the study (Blood. 2017;129:2224-32). The results prompted the U.S. Food and Drug Administration to grant accelerated approval of ibrutinib for patients with MZL who were previously treated with at least one prior anti-CD20–based therapy.

“MZL is frequently linked to chronic infection, which may induce B-cell receptor (BCR) signaling, resulting in aberrant B-cell survival and proliferation,” note the investigators, who were led by Ariela Noy, MD, a hematologic oncologist with the Lymphoma Service at the Memorial Sloan-Kettering Cancer Center, New York. “Single-agent ibrutinib induced durable responses with a favorable benefit–risk profile in patients with previously treated MZL, confirming the role of BCR signaling in this malignancy.”

“As the only approved therapy, ibrutinib provides a treatment option without chemotherapy for MZL,” they maintain. “Future studies will investigate ibrutinib in treatment-naive patients or as combination strategies in relapsed/refractory MZL.”

In the trial, which was funded by Pharmacyclics, an AbbVie Company, patients with MZL of all subtypes who had received at least one prior therapy with an anti-CD20 antibody–containing regimen were treated with 560 mg ibrutinib (Imbruvica) orally once daily. The median number of prior systemic therapies was two, and 63% had received prior chemoimmunotherapy.

The overall response rate, as assessed by an independent review committee using 2007 International Working Group criteria – the trial’s primary endpoint – was 48%, according to the published results. Benefit was similar across patients who differed regarding MZL subtype, number of prior regimen, and previous receipt of chemoimmunotherapy

After a 19.4-month median follow-up, the median duration of response was not reached, and median progression-free survival was 14.2 months.

The most common grade 3 or worse adverse events were anemia (14%), pneumonia (8%), and fatigue (6%). Serious adverse events of any grade affected 44% of patients. The most common was grade 3 or 4 pneumonia. Adverse events led to treatment discontinuation in 17% of patients and dose reductions in 10%.

“Due to evidence of pseudoprogression in our trial … biopsies may be warranted to differentiate between true lymphoma progression and immune-mediated antitumor response,” the investigators note.

Dr. Noy disclosed that she has received research funding from Pharmacyclics.

hematologynews@frontlinemedcom.com

A diagnosis of chronic lymphocytic leukemia (CLL) usually occurs in people aged ≥ 72 years. But most clinical trials do not reflect that reality; thus, treatments and prognoses are based on younger patients’ experiences. Researchers from University of Pennsylvania, Emory University in Georgia, NorthShore University HealthSystem in Illinois, New York-Presbyterian Hospital/Columbia University Medical Center, Thomas Jefferson University in Pennsylvania, and Dana-Farber Cancer Institute in Massachusetts, conducted the largest comprehensive prospective evaluation of this patient population published to date to their knowledge to examine treatment patterns, outcomes, and disease-related mortality in CLL patients aged  ≥ 75 years in a real-world setting.

The researchers analyzed data from patients in the Connect® CLL registry, a prospective observational cohort study that took place between 2010 and 2014 at 199 U.S. sites. Of 1,494 patients enrolled in the registry, 259 patients aged  ≥ 75 years were enrolled within 2 months of starting first- line of therapy (LOT1), and 196 were enrolled in a subsequent line of therapy (LOT ≥ 2). The patients were almost entirely enrolled prior to the introduction of novel B-cell receptor-targeted therapies. The researchers say they aimed to establish a benchmark for outcomes in elderly patients with CLL who were treated before those therapies to help properly position newer agents in the treatment paradigm.

They found that elderly patients with CLL were more likely than were younger patients to receive rituximab monotherapy. In LOT ≥ 2 they were significantly less likely to receive bendamustine/rituximab. Only 6.9% of patients aged > 75 years received fludarabine/cyclophosphamide/rituximab, vs 33.7% of patients aged < 75 years. Interestingly, the researchers add, older patients were significantly more likely than were younger patients to receive chemotherapy alone without anti-CD20 antibody therapy.

Serious adverse events were more common in the elderly patients. Pneumonia was more common in elderly patients in LOT1; in LOT ≥ 2, rates of pneumonia were similar in both groups. In the follow-up with a median of 32.6 months, 433 of the 1,494 patients had died. Only 5% of patients aged < 75 years in LOT1 died of CLL, compared with 13% of elderly patients. Time to death from CLL or infection was also significantly shorter in patients aged > 75 years, compared with patients aged < 75 years. When stratified by risk, mortality due to CLL or infection was 10.3% in the lower risk group compared with 30.6% in the higher risk group.

The researchers identified 3 prognostic indicators: < 3 months from diagnosis to first treatment, enrollment therapy other than bendamustine/rituximab, and anemia. The researchers say the higher risk of CLL- or infection-related death has not, to their knowledge, been reported previously. This finding, they say, “highlights the urgent need for therapies tailored to this population.” Current therapies and strategies, they note, “appear suboptimal.”

Source:
Nabhan C, Mato A, Flowers CR, et al. BMC Cancer. 2017;17(1):198.
doi: 10.1186/s12885-017-3176-x.

A diagnosis of chronic lymphocytic leukemia (CLL) usually occurs in people aged ≥ 72 years. But most clinical trials do not reflect that reality; thus, treatments and prognoses are based on younger patients’ experiences. Researchers from University of Pennsylvania, Emory University in Georgia, NorthShore University HealthSystem in Illinois, New York-Presbyterian Hospital/Columbia University Medical Center, Thomas Jefferson University in Pennsylvania, and Dana-Farber Cancer Institute in Massachusetts, conducted the largest comprehensive prospective evaluation of this patient population published to date to their knowledge to examine treatment patterns, outcomes, and disease-related mortality in CLL patients aged  ≥ 75 years in a real-world setting.

The researchers analyzed data from patients in the Connect® CLL registry, a prospective observational cohort study that took place between 2010 and 2014 at 199 U.S. sites. Of 1,494 patients enrolled in the registry, 259 patients aged  ≥ 75 years were enrolled within 2 months of starting first- line of therapy (LOT1), and 196 were enrolled in a subsequent line of therapy (LOT ≥ 2). The patients were almost entirely enrolled prior to the introduction of novel B-cell receptor-targeted therapies. The researchers say they aimed to establish a benchmark for outcomes in elderly patients with CLL who were treated before those therapies to help properly position newer agents in the treatment paradigm.

They found that elderly patients with CLL were more likely than were younger patients to receive rituximab monotherapy. In LOT ≥ 2 they were significantly less likely to receive bendamustine/rituximab. Only 6.9% of patients aged > 75 years received fludarabine/cyclophosphamide/rituximab, vs 33.7% of patients aged < 75 years. Interestingly, the researchers add, older patients were significantly more likely than were younger patients to receive chemotherapy alone without anti-CD20 antibody therapy.

Serious adverse events were more common in the elderly patients. Pneumonia was more common in elderly patients in LOT1; in LOT ≥ 2, rates of pneumonia were similar in both groups. In the follow-up with a median of 32.6 months, 433 of the 1,494 patients had died. Only 5% of patients aged < 75 years in LOT1 died of CLL, compared with 13% of elderly patients. Time to death from CLL or infection was also significantly shorter in patients aged > 75 years, compared with patients aged < 75 years. When stratified by risk, mortality due to CLL or infection was 10.3% in the lower risk group compared with 30.6% in the higher risk group.

The researchers identified 3 prognostic indicators: < 3 months from diagnosis to first treatment, enrollment therapy other than bendamustine/rituximab, and anemia. The researchers say the higher risk of CLL- or infection-related death has not, to their knowledge, been reported previously. This finding, they say, “highlights the urgent need for therapies tailored to this population.” Current therapies and strategies, they note, “appear suboptimal.”

Source:
Nabhan C, Mato A, Flowers CR, et al. BMC Cancer. 2017;17(1):198.
doi: 10.1186/s12885-017-3176-x.

A diagnosis of chronic lymphocytic leukemia (CLL) usually occurs in people aged ≥ 72 years. But most clinical trials do not reflect that reality; thus, treatments and prognoses are based on younger patients’ experiences. Researchers from University of Pennsylvania, Emory University in Georgia, NorthShore University HealthSystem in Illinois, New York-Presbyterian Hospital/Columbia University Medical Center, Thomas Jefferson University in Pennsylvania, and Dana-Farber Cancer Institute in Massachusetts, conducted the largest comprehensive prospective evaluation of this patient population published to date to their knowledge to examine treatment patterns, outcomes, and disease-related mortality in CLL patients aged  ≥ 75 years in a real-world setting.

The researchers analyzed data from patients in the Connect® CLL registry, a prospective observational cohort study that took place between 2010 and 2014 at 199 U.S. sites. Of 1,494 patients enrolled in the registry, 259 patients aged  ≥ 75 years were enrolled within 2 months of starting first- line of therapy (LOT1), and 196 were enrolled in a subsequent line of therapy (LOT ≥ 2). The patients were almost entirely enrolled prior to the introduction of novel B-cell receptor-targeted therapies. The researchers say they aimed to establish a benchmark for outcomes in elderly patients with CLL who were treated before those therapies to help properly position newer agents in the treatment paradigm.

They found that elderly patients with CLL were more likely than were younger patients to receive rituximab monotherapy. In LOT ≥ 2 they were significantly less likely to receive bendamustine/rituximab. Only 6.9% of patients aged > 75 years received fludarabine/cyclophosphamide/rituximab, vs 33.7% of patients aged < 75 years. Interestingly, the researchers add, older patients were significantly more likely than were younger patients to receive chemotherapy alone without anti-CD20 antibody therapy.

Serious adverse events were more common in the elderly patients. Pneumonia was more common in elderly patients in LOT1; in LOT ≥ 2, rates of pneumonia were similar in both groups. In the follow-up with a median of 32.6 months, 433 of the 1,494 patients had died. Only 5% of patients aged < 75 years in LOT1 died of CLL, compared with 13% of elderly patients. Time to death from CLL or infection was also significantly shorter in patients aged > 75 years, compared with patients aged < 75 years. When stratified by risk, mortality due to CLL or infection was 10.3% in the lower risk group compared with 30.6% in the higher risk group.

The researchers identified 3 prognostic indicators: < 3 months from diagnosis to first treatment, enrollment therapy other than bendamustine/rituximab, and anemia. The researchers say the higher risk of CLL- or infection-related death has not, to their knowledge, been reported previously. This finding, they say, “highlights the urgent need for therapies tailored to this population.” Current therapies and strategies, they note, “appear suboptimal.”

Source:
Nabhan C, Mato A, Flowers CR, et al. BMC Cancer. 2017;17(1):198.
doi: 10.1186/s12885-017-3176-x.

PARIS – Patients hospitalized for heart failure increasingly present with a growing number of noncardiovascular comorbidities, according to registry data from more than 300 U.S. hospitals.

During the decade of 2005-2014, the percentage of patients hospitalized for heart failure diagnosed with three or more noncardiovascular comorbidities (NCCs) jumped from abut 17% of these patients in 2005 to about 28% in 2015, Abhinav Sharma, MD, said at a meeting held by the Heart Failure Association of the ESC. This increase occurred as the percentages of hospitalized heart failure patients with none or one NCC showed clear decreases.

Mitchel L. Zoler/Frontline Medical News

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

PARIS – Patients hospitalized for heart failure increasingly present with a growing number of noncardiovascular comorbidities, according to registry data from more than 300 U.S. hospitals.

During the decade of 2005-2014, the percentage of patients hospitalized for heart failure diagnosed with three or more noncardiovascular comorbidities (NCCs) jumped from abut 17% of these patients in 2005 to about 28% in 2015, Abhinav Sharma, MD, said at a meeting held by the Heart Failure Association of the ESC. This increase occurred as the percentages of hospitalized heart failure patients with none or one NCC showed clear decreases.

Mitchel L. Zoler/Frontline Medical News

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

PARIS – Patients hospitalized for heart failure increasingly present with a growing number of noncardiovascular comorbidities, according to registry data from more than 300 U.S. hospitals.

During the decade of 2005-2014, the percentage of patients hospitalized for heart failure diagnosed with three or more noncardiovascular comorbidities (NCCs) jumped from abut 17% of these patients in 2005 to about 28% in 2015, Abhinav Sharma, MD, said at a meeting held by the Heart Failure Association of the ESC. This increase occurred as the percentages of hospitalized heart failure patients with none or one NCC showed clear decreases.

Mitchel L. Zoler/Frontline Medical News

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

Vibration-controlled transient elastography (VCTE) can accurately diagnose cirrhosis in most patients with chronic liver disease, particularly those with chronic hepatitis B or C, states a new guideline from the AGA Institute, published in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.03.017).

However, magnetic resonance elastography (MRE) is somewhat more accurate for detecting cirrhosis in nonalcoholic fatty liver disease, wrote Joseph K. Lim, MD, AGAF, of Yale University in New Haven, Conn., with his associates from the Clinical Guidelines Committee of the AGA. VCTE is convenient but performs unevenly in some liver conditions and is especially unreliable in patients with acute hepatitis, alcohol abuse, food intake within 2-3 hours, congestive heart failure, or extrahepatic cholestasis, the guideline notes. Yet, VCTE remains the most common imaging tool for diagnosing fibrosis in the United States, and the guideline addresses “focused, clinically relevant questions” to guide its use.

When possible, clinicians should use VCTE instead of noninvasive serum tests for cirrhosis in patients with chronic hepatitis C, the guideline asserts. In pooled analyses of 62 studies, VCTE detected about 89% of cirrhosis cases (95% confidence interval, 84%-92%), Fibrosis-4 test (FIB-4) detected 87% (95% CI, 74%-94%), and aspartate aminotransferase to platelet ratio index (APRI) detected 77% (95% CI, 73%-81%). The specificity of VCTE (91%) also equaled or exceeded that of FIB-4 (91%) or APRI (78%), the guideline noted.

For chronic hepatitis C, MRE had “poorer specificity with higher false-positive rates, suggesting poorer diagnostic performance,” compared with VCTE. Lower cost and lower point-of-care availability make VCTE “an attractive solution compared to MRE,” the guideline adds. It conditionally recommends VCTE cutoffs of 12.5 kPa for cirrhosis and 9.5 kPa for advanced (F3-F4) liver fibrosis after patients have a sustained virologic response to therapy. The 9.5-kPa cutoff would misclassify only 1% of low-risk patients and 7% of high-risk patients, but noncirrhotic patients (less than 9.5 kPa) may reasonably choose to continue specialty care if they prioritize avoiding “the small risk” of hepatocellular carcinoma over the “inconvenience and risks of continued laboratory and fibrosis testing.”

For chronic hepatitis B, the guideline conditionally recommends VCTE with an 11.0-kPa cutoff over APRI or FIB-4. In a pooled analysis of 28 studies, VCTE detected cirrhosis with a sensitivity of 86% and a specificity of 85%, compared with 66% and 74%, respectively, for APRI, and 87% and 65%, respectively, for FIB-4. However, the overall diagnostic performance of VCTE resembled that of the serum tests, and clinicians should interpret VCTE in the context of other clinical cirrhosis data, the guideline states.

Among 17 studies of VCTE cutoffs in hepatitis B, an 11.0-kPa threshold diagnosed cirrhosis with a sensitivity of 81% and a specificity of 83%. This cutoff would miss cirrhosis in less than 1% of low-risk patients and about 5% of high-risk patients and would yield false positives in 10%-15% of patients. Thus, its cutoff minimizes false negatives, reflecting “a judgment that the harm of missing cirrhosis is greater than the harm of over diagnosis,” the authors write.

For chronic alcoholic liver disease, the AGA conditionally recommends VCTE with a cirrhosis cutoff of 12.5 kPa. In pooled analyses, this value had a sensitivity of 95% and a specificity of 71%. For suspected compensated cirrhosis, the guideline conditionally suggests a 19.5-kPa cutoff when assessing the need for esophagogastroduodenoscopy (EGD) to identify high-risk esophageal varices. Patients who fall below this cutoff can reasonably pursue screening endoscopy if they are concerned about the small risk of acute variceal hemorrhage, the guideline adds.

The guideline also conditionally recommends a 17-kPa cutoff to detect clinically significant portal hypertension in patients with suspected chronic liver disease who are undergoing elective nonhepatic surgeries. This cutoff will miss about 0.1% of very low-risk patients, 0.8% of low-risk patients, and 7% of high-risk patients. Because the failure to detect portal hypertension contributes to operative morbidity and mortality, higher-risk patients might “reasonably” pursue screening endoscopy even if their kPa is below the cutoff, the guideline states.

The guideline made no recommendation about VCTE versus APRI or FIB-4 in adults with nonalcoholic fatty liver disease (NAFLD), citing “unacceptable bias” in 12 studies that excluded obese patients, used per-protocol rather than intention-to-diagnose analyses, and ignored “unsuccessful or inadequate” liver stiffness measurements, which are relatively common in NAFLD, the guideline notes. It conditionally recommends MRE over VCTE in high-risk adults with NAFLD, including those who are older, diabetic, or obese (especially with central adiposity) or who have alanine levels more than twice the upper limit of normal. However, it cites insufficient evidence to extend this recommendation to low-risk patients who only have imaging evidence of fatty liver.

Overall, the guideline focuses on “routine clinical management issues, and [does] not address comparisons with proprietary serum fibrosis assays, other emerging imaging-based fibrosis assessment techniques, or combinations of more than one noninvasive fibrosis test,” the authors note. They also limited VCTE cutoffs to single thresholds that prioritized sensitivity over specificity. “Additional studies are needed to further define the role of VCTE, MRE, and emerging diagnostic studies in the assessment of liver fibrosis, for which a significant unmet medical need remains, particularly in conditions such as NAFLD/[nonalcoholic steatohepatitis],” they add. “In particular, defining the implications for serial liver stiffness measurements over time on management decisions is of great interest.”

Dr. Muir has served as a consultant for AbbVie, Bristol-Myers Squibb, Gilead, and Merck. Dr. Lim has served as a consultant for Bristol Myers-Squibb, Gilead, Merck, and Boehringer Ingelheim. Dr. Flamm has served as a consultant or received research support from Gilead, Bristol-Myers Squibb, AbbVie, Salix Pharmaceuticals, and Intercept Pharmaceuticals. Dr. Dieterich has presented lectures for Gilead and Merck products. The rest of the authors disclosed no conflicts related to the content of this guideline.

Vibration-controlled transient elastography (VCTE) can accurately diagnose cirrhosis in most patients with chronic liver disease, particularly those with chronic hepatitis B or C, states a new guideline from the AGA Institute, published in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.03.017).

However, magnetic resonance elastography (MRE) is somewhat more accurate for detecting cirrhosis in nonalcoholic fatty liver disease, wrote Joseph K. Lim, MD, AGAF, of Yale University in New Haven, Conn., with his associates from the Clinical Guidelines Committee of the AGA. VCTE is convenient but performs unevenly in some liver conditions and is especially unreliable in patients with acute hepatitis, alcohol abuse, food intake within 2-3 hours, congestive heart failure, or extrahepatic cholestasis, the guideline notes. Yet, VCTE remains the most common imaging tool for diagnosing fibrosis in the United States, and the guideline addresses “focused, clinically relevant questions” to guide its use.

When possible, clinicians should use VCTE instead of noninvasive serum tests for cirrhosis in patients with chronic hepatitis C, the guideline asserts. In pooled analyses of 62 studies, VCTE detected about 89% of cirrhosis cases (95% confidence interval, 84%-92%), Fibrosis-4 test (FIB-4) detected 87% (95% CI, 74%-94%), and aspartate aminotransferase to platelet ratio index (APRI) detected 77% (95% CI, 73%-81%). The specificity of VCTE (91%) also equaled or exceeded that of FIB-4 (91%) or APRI (78%), the guideline noted.

For chronic hepatitis C, MRE had “poorer specificity with higher false-positive rates, suggesting poorer diagnostic performance,” compared with VCTE. Lower cost and lower point-of-care availability make VCTE “an attractive solution compared to MRE,” the guideline adds. It conditionally recommends VCTE cutoffs of 12.5 kPa for cirrhosis and 9.5 kPa for advanced (F3-F4) liver fibrosis after patients have a sustained virologic response to therapy. The 9.5-kPa cutoff would misclassify only 1% of low-risk patients and 7% of high-risk patients, but noncirrhotic patients (less than 9.5 kPa) may reasonably choose to continue specialty care if they prioritize avoiding “the small risk” of hepatocellular carcinoma over the “inconvenience and risks of continued laboratory and fibrosis testing.”

For chronic hepatitis B, the guideline conditionally recommends VCTE with an 11.0-kPa cutoff over APRI or FIB-4. In a pooled analysis of 28 studies, VCTE detected cirrhosis with a sensitivity of 86% and a specificity of 85%, compared with 66% and 74%, respectively, for APRI, and 87% and 65%, respectively, for FIB-4. However, the overall diagnostic performance of VCTE resembled that of the serum tests, and clinicians should interpret VCTE in the context of other clinical cirrhosis data, the guideline states.

Among 17 studies of VCTE cutoffs in hepatitis B, an 11.0-kPa threshold diagnosed cirrhosis with a sensitivity of 81% and a specificity of 83%. This cutoff would miss cirrhosis in less than 1% of low-risk patients and about 5% of high-risk patients and would yield false positives in 10%-15% of patients. Thus, its cutoff minimizes false negatives, reflecting “a judgment that the harm of missing cirrhosis is greater than the harm of over diagnosis,” the authors write.

For chronic alcoholic liver disease, the AGA conditionally recommends VCTE with a cirrhosis cutoff of 12.5 kPa. In pooled analyses, this value had a sensitivity of 95% and a specificity of 71%. For suspected compensated cirrhosis, the guideline conditionally suggests a 19.5-kPa cutoff when assessing the need for esophagogastroduodenoscopy (EGD) to identify high-risk esophageal varices. Patients who fall below this cutoff can reasonably pursue screening endoscopy if they are concerned about the small risk of acute variceal hemorrhage, the guideline adds.

The guideline also conditionally recommends a 17-kPa cutoff to detect clinically significant portal hypertension in patients with suspected chronic liver disease who are undergoing elective nonhepatic surgeries. This cutoff will miss about 0.1% of very low-risk patients, 0.8% of low-risk patients, and 7% of high-risk patients. Because the failure to detect portal hypertension contributes to operative morbidity and mortality, higher-risk patients might “reasonably” pursue screening endoscopy even if their kPa is below the cutoff, the guideline states.

The guideline made no recommendation about VCTE versus APRI or FIB-4 in adults with nonalcoholic fatty liver disease (NAFLD), citing “unacceptable bias” in 12 studies that excluded obese patients, used per-protocol rather than intention-to-diagnose analyses, and ignored “unsuccessful or inadequate” liver stiffness measurements, which are relatively common in NAFLD, the guideline notes. It conditionally recommends MRE over VCTE in high-risk adults with NAFLD, including those who are older, diabetic, or obese (especially with central adiposity) or who have alanine levels more than twice the upper limit of normal. However, it cites insufficient evidence to extend this recommendation to low-risk patients who only have imaging evidence of fatty liver.

Overall, the guideline focuses on “routine clinical management issues, and [does] not address comparisons with proprietary serum fibrosis assays, other emerging imaging-based fibrosis assessment techniques, or combinations of more than one noninvasive fibrosis test,” the authors note. They also limited VCTE cutoffs to single thresholds that prioritized sensitivity over specificity. “Additional studies are needed to further define the role of VCTE, MRE, and emerging diagnostic studies in the assessment of liver fibrosis, for which a significant unmet medical need remains, particularly in conditions such as NAFLD/[nonalcoholic steatohepatitis],” they add. “In particular, defining the implications for serial liver stiffness measurements over time on management decisions is of great interest.”

Dr. Muir has served as a consultant for AbbVie, Bristol-Myers Squibb, Gilead, and Merck. Dr. Lim has served as a consultant for Bristol Myers-Squibb, Gilead, Merck, and Boehringer Ingelheim. Dr. Flamm has served as a consultant or received research support from Gilead, Bristol-Myers Squibb, AbbVie, Salix Pharmaceuticals, and Intercept Pharmaceuticals. Dr. Dieterich has presented lectures for Gilead and Merck products. The rest of the authors disclosed no conflicts related to the content of this guideline.

Vibration-controlled transient elastography (VCTE) can accurately diagnose cirrhosis in most patients with chronic liver disease, particularly those with chronic hepatitis B or C, states a new guideline from the AGA Institute, published in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.03.017).

However, magnetic resonance elastography (MRE) is somewhat more accurate for detecting cirrhosis in nonalcoholic fatty liver disease, wrote Joseph K. Lim, MD, AGAF, of Yale University in New Haven, Conn., with his associates from the Clinical Guidelines Committee of the AGA. VCTE is convenient but performs unevenly in some liver conditions and is especially unreliable in patients with acute hepatitis, alcohol abuse, food intake within 2-3 hours, congestive heart failure, or extrahepatic cholestasis, the guideline notes. Yet, VCTE remains the most common imaging tool for diagnosing fibrosis in the United States, and the guideline addresses “focused, clinically relevant questions” to guide its use.

When possible, clinicians should use VCTE instead of noninvasive serum tests for cirrhosis in patients with chronic hepatitis C, the guideline asserts. In pooled analyses of 62 studies, VCTE detected about 89% of cirrhosis cases (95% confidence interval, 84%-92%), Fibrosis-4 test (FIB-4) detected 87% (95% CI, 74%-94%), and aspartate aminotransferase to platelet ratio index (APRI) detected 77% (95% CI, 73%-81%). The specificity of VCTE (91%) also equaled or exceeded that of FIB-4 (91%) or APRI (78%), the guideline noted.

For chronic hepatitis C, MRE had “poorer specificity with higher false-positive rates, suggesting poorer diagnostic performance,” compared with VCTE. Lower cost and lower point-of-care availability make VCTE “an attractive solution compared to MRE,” the guideline adds. It conditionally recommends VCTE cutoffs of 12.5 kPa for cirrhosis and 9.5 kPa for advanced (F3-F4) liver fibrosis after patients have a sustained virologic response to therapy. The 9.5-kPa cutoff would misclassify only 1% of low-risk patients and 7% of high-risk patients, but noncirrhotic patients (less than 9.5 kPa) may reasonably choose to continue specialty care if they prioritize avoiding “the small risk” of hepatocellular carcinoma over the “inconvenience and risks of continued laboratory and fibrosis testing.”

For chronic hepatitis B, the guideline conditionally recommends VCTE with an 11.0-kPa cutoff over APRI or FIB-4. In a pooled analysis of 28 studies, VCTE detected cirrhosis with a sensitivity of 86% and a specificity of 85%, compared with 66% and 74%, respectively, for APRI, and 87% and 65%, respectively, for FIB-4. However, the overall diagnostic performance of VCTE resembled that of the serum tests, and clinicians should interpret VCTE in the context of other clinical cirrhosis data, the guideline states.

Among 17 studies of VCTE cutoffs in hepatitis B, an 11.0-kPa threshold diagnosed cirrhosis with a sensitivity of 81% and a specificity of 83%. This cutoff would miss cirrhosis in less than 1% of low-risk patients and about 5% of high-risk patients and would yield false positives in 10%-15% of patients. Thus, its cutoff minimizes false negatives, reflecting “a judgment that the harm of missing cirrhosis is greater than the harm of over diagnosis,” the authors write.

For chronic alcoholic liver disease, the AGA conditionally recommends VCTE with a cirrhosis cutoff of 12.5 kPa. In pooled analyses, this value had a sensitivity of 95% and a specificity of 71%. For suspected compensated cirrhosis, the guideline conditionally suggests a 19.5-kPa cutoff when assessing the need for esophagogastroduodenoscopy (EGD) to identify high-risk esophageal varices. Patients who fall below this cutoff can reasonably pursue screening endoscopy if they are concerned about the small risk of acute variceal hemorrhage, the guideline adds.

The guideline also conditionally recommends a 17-kPa cutoff to detect clinically significant portal hypertension in patients with suspected chronic liver disease who are undergoing elective nonhepatic surgeries. This cutoff will miss about 0.1% of very low-risk patients, 0.8% of low-risk patients, and 7% of high-risk patients. Because the failure to detect portal hypertension contributes to operative morbidity and mortality, higher-risk patients might “reasonably” pursue screening endoscopy even if their kPa is below the cutoff, the guideline states.

The guideline made no recommendation about VCTE versus APRI or FIB-4 in adults with nonalcoholic fatty liver disease (NAFLD), citing “unacceptable bias” in 12 studies that excluded obese patients, used per-protocol rather than intention-to-diagnose analyses, and ignored “unsuccessful or inadequate” liver stiffness measurements, which are relatively common in NAFLD, the guideline notes. It conditionally recommends MRE over VCTE in high-risk adults with NAFLD, including those who are older, diabetic, or obese (especially with central adiposity) or who have alanine levels more than twice the upper limit of normal. However, it cites insufficient evidence to extend this recommendation to low-risk patients who only have imaging evidence of fatty liver.

Overall, the guideline focuses on “routine clinical management issues, and [does] not address comparisons with proprietary serum fibrosis assays, other emerging imaging-based fibrosis assessment techniques, or combinations of more than one noninvasive fibrosis test,” the authors note. They also limited VCTE cutoffs to single thresholds that prioritized sensitivity over specificity. “Additional studies are needed to further define the role of VCTE, MRE, and emerging diagnostic studies in the assessment of liver fibrosis, for which a significant unmet medical need remains, particularly in conditions such as NAFLD/[nonalcoholic steatohepatitis],” they add. “In particular, defining the implications for serial liver stiffness measurements over time on management decisions is of great interest.”

Dr. Muir has served as a consultant for AbbVie, Bristol-Myers Squibb, Gilead, and Merck. Dr. Lim has served as a consultant for Bristol Myers-Squibb, Gilead, Merck, and Boehringer Ingelheim. Dr. Flamm has served as a consultant or received research support from Gilead, Bristol-Myers Squibb, AbbVie, Salix Pharmaceuticals, and Intercept Pharmaceuticals. Dr. Dieterich has presented lectures for Gilead and Merck products. The rest of the authors disclosed no conflicts related to the content of this guideline.

The AGA Institute issued a clinical practice update for managing hepatitis C virus–infected patients who achieve a sustained virologic response after antiviral therapy, who still require ongoing care for their liver disease. The expert review appears in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.03.018).

Even though direct-acting antiviral regimens have produced remarkably high sustained virologic response (SVR) rates and it appears that fewer than 1% of patients relapse, and even though liver fibrosis and cirrhosis may regress with this therapy, continued surveillance and even intervention may be needed “to reduce complications arising from liver damage that has already accrued by the time SVR was attained,” said Ira M. Jacobson, MD, AGAF, chair of the department of medicine, Mount Sinai Beth Israel Medical Center, New York, and his associates.

The AGA Institute issued a clinical practice update for managing hepatitis C virus–infected patients who achieve a sustained virologic response after antiviral therapy, who still require ongoing care for their liver disease. The expert review appears in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.03.018).

Even though direct-acting antiviral regimens have produced remarkably high sustained virologic response (SVR) rates and it appears that fewer than 1% of patients relapse, and even though liver fibrosis and cirrhosis may regress with this therapy, continued surveillance and even intervention may be needed “to reduce complications arising from liver damage that has already accrued by the time SVR was attained,” said Ira M. Jacobson, MD, AGAF, chair of the department of medicine, Mount Sinai Beth Israel Medical Center, New York, and his associates.

The AGA Institute issued a clinical practice update for managing hepatitis C virus–infected patients who achieve a sustained virologic response after antiviral therapy, who still require ongoing care for their liver disease. The expert review appears in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.03.018).

Even though direct-acting antiviral regimens have produced remarkably high sustained virologic response (SVR) rates and it appears that fewer than 1% of patients relapse, and even though liver fibrosis and cirrhosis may regress with this therapy, continued surveillance and even intervention may be needed “to reduce complications arising from liver damage that has already accrued by the time SVR was attained,” said Ira M. Jacobson, MD, AGAF, chair of the department of medicine, Mount Sinai Beth Israel Medical Center, New York, and his associates.