AVAHO

HOUSTON – A novel anti-CD45 targeted conditioning regimen is feasible for use in older patients with relapsed or refractory acute myeloid leukemia undergoing transplant, according to preliminary results of a randomized, phase 3 trial.

Treatment with iodine-131 apamistamab (Iomab-B) has thus far has resulted in successful engraftment for all patients who have received it and gone on to transplant, despite active disease and high bone marrow blast burden prior to transplantation, according to Sergio A. Giralt, MD, of Memorial Sloan Kettering Cancer Center, New York.

There has been no nonrelapse mortality related to the novel regimen in the ongoing trial, which compares Iomab-B as targeted conditioning prior to allogeneic hematopoietic stem cell transplant (HCT) with standard of care regimens, Dr. Giralt said in an update on the trial, known as SIERRA.

SIERRA is the only ongoing, randomized, phase 3 clinical trial to offer a transplant option in patients aged 55 years or older with active relapsed or refractory acute myeloid leukemia (AML), Dr. Giralt said at the Transplantation & Cellular Therapy Meetings.

“This is an underserved population in which traditional transplant techniques have very poor results, and there are limited options for patients with active disease,” Dr. Giralt said. “Of note, many transplant centers today do not consider these patients eligible for transplant.”

A total of 150 patients are to be enrolled in SIERRA and randomized either to investigator’s choice of salvage induction chemotherapy including approved targeted agents or to the experimental arm, which consists of an individualized dose of Iomab-B 12 days prior to HCT with fludarabine and total body irradiation as transplant conditioning.

Dr. Giralt presented an update on the first 38 patients in SIERRA, representing 25% of the total enrollment target.

Of 18 patients randomized to Iomab-B and transplanted, the median number of days to absolute neutrophil count engraftment was 13, Dr. Giralt said.

In the control arm, 15 of 19 (79%) failed to achieve complete remission, and of those 10 crossed over to receive Iomab-B and transplant. Days to engraftment, full donor chimerism, and dose delivered to the bone marrow were all similar in the crossover group, compared with those initially randomized to the novel therapy.

Nonhematologic grade 3 or 4 toxicities were similar between the Iomab-B arm and the conventional care arm, and included febrile neutropenia, stomatitis, and other side effects typical for these patients.

There were no grade 3 or 4 Iomab-B infusion-related reactions, and four mild cases of chronic graft-versus-host disease occurred in Iomab-B treated patients.

Nonrelapse mortality was “extremely low” with no cases in the 100 days post transplant in those initially randomized to Iomab-B, and only one case in a crossover patient, Dr. Giralt said.

“These results are encouraging, and can broaden transplant eligibility and improve outcomes,” he added.

The meeting is held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

The SIERRA study is supported by Actinium Pharmaceuticals. Dr. Giralt reported disclosures related to Actinium and several other companies.

SOURCE: Giralt SA et al. TCT 2019, Abstract LBA3.

HOUSTON – A novel anti-CD45 targeted conditioning regimen is feasible for use in older patients with relapsed or refractory acute myeloid leukemia undergoing transplant, according to preliminary results of a randomized, phase 3 trial.

Treatment with iodine-131 apamistamab (Iomab-B) has thus far has resulted in successful engraftment for all patients who have received it and gone on to transplant, despite active disease and high bone marrow blast burden prior to transplantation, according to Sergio A. Giralt, MD, of Memorial Sloan Kettering Cancer Center, New York.

There has been no nonrelapse mortality related to the novel regimen in the ongoing trial, which compares Iomab-B as targeted conditioning prior to allogeneic hematopoietic stem cell transplant (HCT) with standard of care regimens, Dr. Giralt said in an update on the trial, known as SIERRA.

SIERRA is the only ongoing, randomized, phase 3 clinical trial to offer a transplant option in patients aged 55 years or older with active relapsed or refractory acute myeloid leukemia (AML), Dr. Giralt said at the Transplantation & Cellular Therapy Meetings.

“This is an underserved population in which traditional transplant techniques have very poor results, and there are limited options for patients with active disease,” Dr. Giralt said. “Of note, many transplant centers today do not consider these patients eligible for transplant.”

A total of 150 patients are to be enrolled in SIERRA and randomized either to investigator’s choice of salvage induction chemotherapy including approved targeted agents or to the experimental arm, which consists of an individualized dose of Iomab-B 12 days prior to HCT with fludarabine and total body irradiation as transplant conditioning.

Dr. Giralt presented an update on the first 38 patients in SIERRA, representing 25% of the total enrollment target.

Of 18 patients randomized to Iomab-B and transplanted, the median number of days to absolute neutrophil count engraftment was 13, Dr. Giralt said.

In the control arm, 15 of 19 (79%) failed to achieve complete remission, and of those 10 crossed over to receive Iomab-B and transplant. Days to engraftment, full donor chimerism, and dose delivered to the bone marrow were all similar in the crossover group, compared with those initially randomized to the novel therapy.

Nonhematologic grade 3 or 4 toxicities were similar between the Iomab-B arm and the conventional care arm, and included febrile neutropenia, stomatitis, and other side effects typical for these patients.

There were no grade 3 or 4 Iomab-B infusion-related reactions, and four mild cases of chronic graft-versus-host disease occurred in Iomab-B treated patients.

Nonrelapse mortality was “extremely low” with no cases in the 100 days post transplant in those initially randomized to Iomab-B, and only one case in a crossover patient, Dr. Giralt said.

“These results are encouraging, and can broaden transplant eligibility and improve outcomes,” he added.

The meeting is held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

The SIERRA study is supported by Actinium Pharmaceuticals. Dr. Giralt reported disclosures related to Actinium and several other companies.

SOURCE: Giralt SA et al. TCT 2019, Abstract LBA3.

HOUSTON – A novel anti-CD45 targeted conditioning regimen is feasible for use in older patients with relapsed or refractory acute myeloid leukemia undergoing transplant, according to preliminary results of a randomized, phase 3 trial.

Treatment with iodine-131 apamistamab (Iomab-B) has thus far has resulted in successful engraftment for all patients who have received it and gone on to transplant, despite active disease and high bone marrow blast burden prior to transplantation, according to Sergio A. Giralt, MD, of Memorial Sloan Kettering Cancer Center, New York.

There has been no nonrelapse mortality related to the novel regimen in the ongoing trial, which compares Iomab-B as targeted conditioning prior to allogeneic hematopoietic stem cell transplant (HCT) with standard of care regimens, Dr. Giralt said in an update on the trial, known as SIERRA.

SIERRA is the only ongoing, randomized, phase 3 clinical trial to offer a transplant option in patients aged 55 years or older with active relapsed or refractory acute myeloid leukemia (AML), Dr. Giralt said at the Transplantation & Cellular Therapy Meetings.

“This is an underserved population in which traditional transplant techniques have very poor results, and there are limited options for patients with active disease,” Dr. Giralt said. “Of note, many transplant centers today do not consider these patients eligible for transplant.”

A total of 150 patients are to be enrolled in SIERRA and randomized either to investigator’s choice of salvage induction chemotherapy including approved targeted agents or to the experimental arm, which consists of an individualized dose of Iomab-B 12 days prior to HCT with fludarabine and total body irradiation as transplant conditioning.

Dr. Giralt presented an update on the first 38 patients in SIERRA, representing 25% of the total enrollment target.

Of 18 patients randomized to Iomab-B and transplanted, the median number of days to absolute neutrophil count engraftment was 13, Dr. Giralt said.

In the control arm, 15 of 19 (79%) failed to achieve complete remission, and of those 10 crossed over to receive Iomab-B and transplant. Days to engraftment, full donor chimerism, and dose delivered to the bone marrow were all similar in the crossover group, compared with those initially randomized to the novel therapy.

Nonhematologic grade 3 or 4 toxicities were similar between the Iomab-B arm and the conventional care arm, and included febrile neutropenia, stomatitis, and other side effects typical for these patients.

There were no grade 3 or 4 Iomab-B infusion-related reactions, and four mild cases of chronic graft-versus-host disease occurred in Iomab-B treated patients.

Nonrelapse mortality was “extremely low” with no cases in the 100 days post transplant in those initially randomized to Iomab-B, and only one case in a crossover patient, Dr. Giralt said.

“These results are encouraging, and can broaden transplant eligibility and improve outcomes,” he added.

The meeting is held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

The SIERRA study is supported by Actinium Pharmaceuticals. Dr. Giralt reported disclosures related to Actinium and several other companies.

SOURCE: Giralt SA et al. TCT 2019, Abstract LBA3.

The Food and Drug Administration has approved Trazimera (trastuzumab-qyyp), a biosimilar of Herceptin (trastuzumab), for the treatment of HER2-positive breast cancer and HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma.

FDA approval was based on a review of a comprehensive data package, which included results from the REFLECTIONS B327-02 trial. In this trial, Trazimera was found to have clinical equivalence with trastuzumab in the first-line treatment setting in patients with HER2-positive metastatic breast cancer.

The most common adverse events associated with Trazimera in patients with breast cancer include fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, shortness of breath, rash, low white and red blood cell counts, and muscle pain. For patients with metastatic adenocarcinoma, the most common adverse events include low white and red blood cell counts; diarrhea; fatigue; swelling of the mouth lining, mucous membranes, nose, or throat; weight loss; upper respiratory tract infections; fever; low platelet counts; and change in taste.

“Approximately 15-30% of breast cancers and 10-30% of gastric cancers are HER2-positive, which is associated with aggressive disease and poor prognoses for patients. With the availability of biosimilars like Trazimera in the U.S., oncologists will have additional treatment options to choose from, which may help provide patients with greater access to the medicines they need,” Mark Pegram, MD, director of the breast oncology program at the Stanford Women’s Cancer Center at Stanford (Calif.) University, said in the press release.

Find the full press release on the Pfizer website.

lfranki@mdedge.com

The Food and Drug Administration has approved Trazimera (trastuzumab-qyyp), a biosimilar of Herceptin (trastuzumab), for the treatment of HER2-positive breast cancer and HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma.

FDA approval was based on a review of a comprehensive data package, which included results from the REFLECTIONS B327-02 trial. In this trial, Trazimera was found to have clinical equivalence with trastuzumab in the first-line treatment setting in patients with HER2-positive metastatic breast cancer.

The most common adverse events associated with Trazimera in patients with breast cancer include fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, shortness of breath, rash, low white and red blood cell counts, and muscle pain. For patients with metastatic adenocarcinoma, the most common adverse events include low white and red blood cell counts; diarrhea; fatigue; swelling of the mouth lining, mucous membranes, nose, or throat; weight loss; upper respiratory tract infections; fever; low platelet counts; and change in taste.

“Approximately 15-30% of breast cancers and 10-30% of gastric cancers are HER2-positive, which is associated with aggressive disease and poor prognoses for patients. With the availability of biosimilars like Trazimera in the U.S., oncologists will have additional treatment options to choose from, which may help provide patients with greater access to the medicines they need,” Mark Pegram, MD, director of the breast oncology program at the Stanford Women’s Cancer Center at Stanford (Calif.) University, said in the press release.

Find the full press release on the Pfizer website.

lfranki@mdedge.com

The Food and Drug Administration has approved Trazimera (trastuzumab-qyyp), a biosimilar of Herceptin (trastuzumab), for the treatment of HER2-positive breast cancer and HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma.

FDA approval was based on a review of a comprehensive data package, which included results from the REFLECTIONS B327-02 trial. In this trial, Trazimera was found to have clinical equivalence with trastuzumab in the first-line treatment setting in patients with HER2-positive metastatic breast cancer.

The most common adverse events associated with Trazimera in patients with breast cancer include fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, shortness of breath, rash, low white and red blood cell counts, and muscle pain. For patients with metastatic adenocarcinoma, the most common adverse events include low white and red blood cell counts; diarrhea; fatigue; swelling of the mouth lining, mucous membranes, nose, or throat; weight loss; upper respiratory tract infections; fever; low platelet counts; and change in taste.

“Approximately 15-30% of breast cancers and 10-30% of gastric cancers are HER2-positive, which is associated with aggressive disease and poor prognoses for patients. With the availability of biosimilars like Trazimera in the U.S., oncologists will have additional treatment options to choose from, which may help provide patients with greater access to the medicines they need,” Mark Pegram, MD, director of the breast oncology program at the Stanford Women’s Cancer Center at Stanford (Calif.) University, said in the press release.

Find the full press release on the Pfizer website.

lfranki@mdedge.com

HONOLULU – During the first month after a new cancer diagnosis, patients face a substantially elevated risk for an arterial thromboembolic event – an MI or stroke – consistent with the well-described increased risk newly diagnosed cancer patients face from venous thromboembolism, based on findings from a prospective study of more than 4,000 people.

In the new study, 836 patients newly diagnosed with cancer had a 480% increased rate of a fatal or nonfatal MI or stroke during the 30 days following their diagnosis, compared with 3,339 matched people without cancer and after adjustment for baseline differences in demographics and cardiovascular risk factors, Babak B. Navi, MD, said while presenting a poster at the International Stroke Conference sponsored by the American Heart Association.

An additional analysis that focused on 210 of the 836 patients with incident cancer who had any of seven of the cancers known to pose the highest venous thromboembolism risk (lymphoma; gynecologic cancer; or cancer of the pancreas, stomach, lung, bladder, or testes) showed an 1,750% greater rate of incident MI or stroke during the first 30 days after diagnosis, compared with matched people without cancer, reported Dr. Navi, chief of the stroke and hospital neurology at Weill Cornell Medicine, New York.

In contrast, during both the period 1-3 months after the cancer diagnosis and more than 3 months after, the rate of MI or stroke among recently diagnosed cancer patients was not significantly different from the rate in comparator individuals, although the data showed modest trends toward more arterial thromboembolic events after a month, and the lack of statistically significant differences may have been a power issue, Dr. Navi suggested.

Mitchel L. Zoler/MDedge News

Dr. Navi and his associates designed this study to validate previously reported findings of increased arterial thromboembolic events in newly diagnosed cancer patients from studies of insurance claims databases. Although the increased risk for venous thromboembolism in cancer patients is already well established, documenting a similar risk for arterial events is important because they are “generally more impactful for patients than venous thromboembolism,” Dr. Navi said.

REGARDS has received no commercial funding. Dr. Navi reported no disclosures.

mzoler@mdedge.com

SOURCE: Navi BB et al. Stroke. 2019 Feb;50(Suppl_1): Abstract WMP53.

HONOLULU – During the first month after a new cancer diagnosis, patients face a substantially elevated risk for an arterial thromboembolic event – an MI or stroke – consistent with the well-described increased risk newly diagnosed cancer patients face from venous thromboembolism, based on findings from a prospective study of more than 4,000 people.

In the new study, 836 patients newly diagnosed with cancer had a 480% increased rate of a fatal or nonfatal MI or stroke during the 30 days following their diagnosis, compared with 3,339 matched people without cancer and after adjustment for baseline differences in demographics and cardiovascular risk factors, Babak B. Navi, MD, said while presenting a poster at the International Stroke Conference sponsored by the American Heart Association.

An additional analysis that focused on 210 of the 836 patients with incident cancer who had any of seven of the cancers known to pose the highest venous thromboembolism risk (lymphoma; gynecologic cancer; or cancer of the pancreas, stomach, lung, bladder, or testes) showed an 1,750% greater rate of incident MI or stroke during the first 30 days after diagnosis, compared with matched people without cancer, reported Dr. Navi, chief of the stroke and hospital neurology at Weill Cornell Medicine, New York.

In contrast, during both the period 1-3 months after the cancer diagnosis and more than 3 months after, the rate of MI or stroke among recently diagnosed cancer patients was not significantly different from the rate in comparator individuals, although the data showed modest trends toward more arterial thromboembolic events after a month, and the lack of statistically significant differences may have been a power issue, Dr. Navi suggested.

Mitchel L. Zoler/MDedge News

Dr. Navi and his associates designed this study to validate previously reported findings of increased arterial thromboembolic events in newly diagnosed cancer patients from studies of insurance claims databases. Although the increased risk for venous thromboembolism in cancer patients is already well established, documenting a similar risk for arterial events is important because they are “generally more impactful for patients than venous thromboembolism,” Dr. Navi said.

REGARDS has received no commercial funding. Dr. Navi reported no disclosures.

mzoler@mdedge.com

SOURCE: Navi BB et al. Stroke. 2019 Feb;50(Suppl_1): Abstract WMP53.

HONOLULU – During the first month after a new cancer diagnosis, patients face a substantially elevated risk for an arterial thromboembolic event – an MI or stroke – consistent with the well-described increased risk newly diagnosed cancer patients face from venous thromboembolism, based on findings from a prospective study of more than 4,000 people.

In the new study, 836 patients newly diagnosed with cancer had a 480% increased rate of a fatal or nonfatal MI or stroke during the 30 days following their diagnosis, compared with 3,339 matched people without cancer and after adjustment for baseline differences in demographics and cardiovascular risk factors, Babak B. Navi, MD, said while presenting a poster at the International Stroke Conference sponsored by the American Heart Association.

An additional analysis that focused on 210 of the 836 patients with incident cancer who had any of seven of the cancers known to pose the highest venous thromboembolism risk (lymphoma; gynecologic cancer; or cancer of the pancreas, stomach, lung, bladder, or testes) showed an 1,750% greater rate of incident MI or stroke during the first 30 days after diagnosis, compared with matched people without cancer, reported Dr. Navi, chief of the stroke and hospital neurology at Weill Cornell Medicine, New York.

In contrast, during both the period 1-3 months after the cancer diagnosis and more than 3 months after, the rate of MI or stroke among recently diagnosed cancer patients was not significantly different from the rate in comparator individuals, although the data showed modest trends toward more arterial thromboembolic events after a month, and the lack of statistically significant differences may have been a power issue, Dr. Navi suggested.

Mitchel L. Zoler/MDedge News

Dr. Navi and his associates designed this study to validate previously reported findings of increased arterial thromboembolic events in newly diagnosed cancer patients from studies of insurance claims databases. Although the increased risk for venous thromboembolism in cancer patients is already well established, documenting a similar risk for arterial events is important because they are “generally more impactful for patients than venous thromboembolism,” Dr. Navi said.

REGARDS has received no commercial funding. Dr. Navi reported no disclosures.

mzoler@mdedge.com

SOURCE: Navi BB et al. Stroke. 2019 Feb;50(Suppl_1): Abstract WMP53.

Endoscopic full-thickness resection (EFTR) may be an effective treatment strategy for patients with early colorectal cancer, according to results from a study published in Gastrointestinal Endoscopy.

“EFTR is an emerging technique for removal of nonlifting colorectal lesions but data on resection of malignant tumors are limited,” wrote Armin Kuellmer, MD, of the University of Freiburg (Germany), along with his colleagues.

The researchers retrospectively studied a cohort of 156 patients with histologically confirmed adenocarcinoma from 2015 to 2018 included in a German endoscopy registry. The most common indication for the procedure was removal of nonlifting lesions (n = 92), followed by resection of malignant polyps (n = 64). Dr. Kuellmer and his colleagues examined the efficacy, safety, and clinical significance of this novel technique.

The primary outcomes measured were technical success and R0 resection, which were defined as the macroscopic complete removal of the lesion and complete histologic removal with no evidence of malignant tissue in a tissue sample, respectively.

“Low-risk versus high-risk lesions are difficult to discriminate before resection as criteria are based on histological features,” the researchers wrote. “The study underlines the potential of EFTR to exactly discriminate between high-risk versus low-risk tumors to aid decision[s] for the optimal individual treatment strategy.”

After analysis, the investigators reported a technical success rate of 92.3% in patients who underwent the procedure and that the R0 resection rate was 71.8% in the same group.

“Reported technical success rates of EFTR for other indications [mainly nonlifting adenomas] range from 75% to 100% and are in line with our data,” they explained.

In a subgroup analysis, Dr. Kuellmer and his colleagues saw a higher R0 resection rate in patients who underwent the procedure for removal of malignant polyps (group 1) versus nonlifting lesions (group 2) (87.5% vs. 60.9%; P less than .001).

“This [difference] may be due to the fact that group 1 mainly consisted of low-risk tumors and small resection scars whereas the majority of lesions in group 2 proved to be more advanced tumors,” they added.

With respect to safety, 21 treatment-related adverse events were seen in the cohort, which were classified as either mild, moderate, or severe. Of these events, six were severe, defined as possibly life-threatening or requiring surgical intervention to resolve.

“The rate of major [adverse events] including perforation is in line with reported data on EFTR for other indications [0%-5%],” they wrote.

The authors acknowledged that a key limitation of the study was the retrospective cohort design. As a result, specific treatment strategies and procedural expertise could have varied across the participating centers. “We therefore cannot provide data on how much patients in total have been evaluated for EFTR,” they wrote.

Moving forward, the researchers highlighted the importance of conducting prospective studies to assess whether EFTR is a viable, safe, and effective treatment option for patients with early colorectal cancer.

“For patients with high-risk lesions unfit for surgery, [EFTR] might as well be a valuable option for local endoscopic treatment,” they concluded.

Funding sources and conflicts of interests were not reported.

SOURCE: Kuellmer A et al. Gastrointest Endosc. 2019 Jan 14. doi: 10.1016/j.gie.2018.12.025.

Endoscopic full-thickness resection (EFTR) may be an effective treatment strategy for patients with early colorectal cancer, according to results from a study published in Gastrointestinal Endoscopy.

“EFTR is an emerging technique for removal of nonlifting colorectal lesions but data on resection of malignant tumors are limited,” wrote Armin Kuellmer, MD, of the University of Freiburg (Germany), along with his colleagues.

The researchers retrospectively studied a cohort of 156 patients with histologically confirmed adenocarcinoma from 2015 to 2018 included in a German endoscopy registry. The most common indication for the procedure was removal of nonlifting lesions (n = 92), followed by resection of malignant polyps (n = 64). Dr. Kuellmer and his colleagues examined the efficacy, safety, and clinical significance of this novel technique.

The primary outcomes measured were technical success and R0 resection, which were defined as the macroscopic complete removal of the lesion and complete histologic removal with no evidence of malignant tissue in a tissue sample, respectively.

“Low-risk versus high-risk lesions are difficult to discriminate before resection as criteria are based on histological features,” the researchers wrote. “The study underlines the potential of EFTR to exactly discriminate between high-risk versus low-risk tumors to aid decision[s] for the optimal individual treatment strategy.”

After analysis, the investigators reported a technical success rate of 92.3% in patients who underwent the procedure and that the R0 resection rate was 71.8% in the same group.

“Reported technical success rates of EFTR for other indications [mainly nonlifting adenomas] range from 75% to 100% and are in line with our data,” they explained.

In a subgroup analysis, Dr. Kuellmer and his colleagues saw a higher R0 resection rate in patients who underwent the procedure for removal of malignant polyps (group 1) versus nonlifting lesions (group 2) (87.5% vs. 60.9%; P less than .001).

“This [difference] may be due to the fact that group 1 mainly consisted of low-risk tumors and small resection scars whereas the majority of lesions in group 2 proved to be more advanced tumors,” they added.

With respect to safety, 21 treatment-related adverse events were seen in the cohort, which were classified as either mild, moderate, or severe. Of these events, six were severe, defined as possibly life-threatening or requiring surgical intervention to resolve.

“The rate of major [adverse events] including perforation is in line with reported data on EFTR for other indications [0%-5%],” they wrote.

The authors acknowledged that a key limitation of the study was the retrospective cohort design. As a result, specific treatment strategies and procedural expertise could have varied across the participating centers. “We therefore cannot provide data on how much patients in total have been evaluated for EFTR,” they wrote.

Moving forward, the researchers highlighted the importance of conducting prospective studies to assess whether EFTR is a viable, safe, and effective treatment option for patients with early colorectal cancer.

“For patients with high-risk lesions unfit for surgery, [EFTR] might as well be a valuable option for local endoscopic treatment,” they concluded.

Funding sources and conflicts of interests were not reported.

SOURCE: Kuellmer A et al. Gastrointest Endosc. 2019 Jan 14. doi: 10.1016/j.gie.2018.12.025.

Endoscopic full-thickness resection (EFTR) may be an effective treatment strategy for patients with early colorectal cancer, according to results from a study published in Gastrointestinal Endoscopy.

“EFTR is an emerging technique for removal of nonlifting colorectal lesions but data on resection of malignant tumors are limited,” wrote Armin Kuellmer, MD, of the University of Freiburg (Germany), along with his colleagues.

The researchers retrospectively studied a cohort of 156 patients with histologically confirmed adenocarcinoma from 2015 to 2018 included in a German endoscopy registry. The most common indication for the procedure was removal of nonlifting lesions (n = 92), followed by resection of malignant polyps (n = 64). Dr. Kuellmer and his colleagues examined the efficacy, safety, and clinical significance of this novel technique.

The primary outcomes measured were technical success and R0 resection, which were defined as the macroscopic complete removal of the lesion and complete histologic removal with no evidence of malignant tissue in a tissue sample, respectively.

“Low-risk versus high-risk lesions are difficult to discriminate before resection as criteria are based on histological features,” the researchers wrote. “The study underlines the potential of EFTR to exactly discriminate between high-risk versus low-risk tumors to aid decision[s] for the optimal individual treatment strategy.”

After analysis, the investigators reported a technical success rate of 92.3% in patients who underwent the procedure and that the R0 resection rate was 71.8% in the same group.

“Reported technical success rates of EFTR for other indications [mainly nonlifting adenomas] range from 75% to 100% and are in line with our data,” they explained.

In a subgroup analysis, Dr. Kuellmer and his colleagues saw a higher R0 resection rate in patients who underwent the procedure for removal of malignant polyps (group 1) versus nonlifting lesions (group 2) (87.5% vs. 60.9%; P less than .001).

“This [difference] may be due to the fact that group 1 mainly consisted of low-risk tumors and small resection scars whereas the majority of lesions in group 2 proved to be more advanced tumors,” they added.

With respect to safety, 21 treatment-related adverse events were seen in the cohort, which were classified as either mild, moderate, or severe. Of these events, six were severe, defined as possibly life-threatening or requiring surgical intervention to resolve.

“The rate of major [adverse events] including perforation is in line with reported data on EFTR for other indications [0%-5%],” they wrote.

The authors acknowledged that a key limitation of the study was the retrospective cohort design. As a result, specific treatment strategies and procedural expertise could have varied across the participating centers. “We therefore cannot provide data on how much patients in total have been evaluated for EFTR,” they wrote.

Moving forward, the researchers highlighted the importance of conducting prospective studies to assess whether EFTR is a viable, safe, and effective treatment option for patients with early colorectal cancer.

“For patients with high-risk lesions unfit for surgery, [EFTR] might as well be a valuable option for local endoscopic treatment,” they concluded.

Funding sources and conflicts of interests were not reported.

SOURCE: Kuellmer A et al. Gastrointest Endosc. 2019 Jan 14. doi: 10.1016/j.gie.2018.12.025.

A proposed clinical scoring system using readily available laboratory data, rather than complex formulas, can be used to predict risk for overall survival and help with clinical decision making for patients with multiple myeloma who are ineligible for stem cell transplants, the system’s creators claim.

Peter Anderson/ Pathology Education Informational Resource Digital Library/copyright University of Alabama at Birmingham, Department of Pathology

When applied to data from two clinical trials that enrolled patients with transplant-ineligible multiple myeloma, the UK Myeloma Research Alliance Risk Profile (MRP) was shown to accurately group patients into low-, medium- and high-risk categories and was prognostic of overall survival, reported Gordon Cook, PhD, of the University of Leeds, England, and his colleagues.

“The ability of clinical scoring systems, such as that proposed here, to predict whether a patient is likely to stop treatment early because of treatment intolerability, could enable preemptive, upfront dose adjustments in patients with multiple myeloma, preventing toxicity and potentially enabling patients to stay on therapy for longer,” they wrote in the Lancet Haematology.

The investigators used data on 1,852 newly diagnosed patients recruited to the non–intensive treatment pathway of the UK’s National Cancer Research Institute Myeloma XI study (NCRI-XI, ISRCTN49407852) for a training dataset and internal validation dataset, and 520 patients recruited into the Medical Research Council Myeloma IX study (MRC-IX, ISRCTN68454111) for the test dataset.

Patient characteristics, biochemical measurements, and hematological data were plugged into univariate and multivariate models to determine their potential as prognostic variables.

The final model for the test and validation datasets included World Health Organization performance status, the multiple myeloma International Staging System, patient age, and C-reactive protein concentrations.

As noted before, the scoring algorithm groups patients into low-, medium- and high-risk categories, with each of the prognostic variables increasing in severity across the three groups in both clinical trials.

In the NCRI-XI trial, median overall survival for patients in the MRP low-risk group was 60 months, compared with 44 months in the medium-risk group, and 25 months in the high-risk group.

Similarly, in the MRC-IX trial, the respective median overall survival was 49, 34, and 20 months.

The risk groups also were associated with progression-free survival in each trial, although not as robustly as the association with overall survival.

The investigators also found that, the higher the risk group, the greater the likelihood that the median percentage of protocol dose delivered would be lower, and both a decrease in protocol dose delivered and quality of life at baseline were associated with increased risk.

The MRP categories were prognostic in patients treated with various therapeutic regimens and in patients with high-risk cytogenetics.

“None of the risk scoring systems previously developed in myeloma are dynamic, making them unable to accommodate changes in disease-related frailty that might be minimized by effective anti-myeloma therapy. There is therefore scope to improve clinical risk scores by the addition of a suitable frailty biomarker, which is currently still in developmental stages,” Dr. Cook and his colleagues wrote.

The study was funded by the Medical Research Council, Novartis, Schering Health Care, Chugai, Pharmion, Celgene, Ortho Biotech, Cancer Research UK, Celgene, Merck Sharp & Dohme, and Amgen. Dr. Cook reported grants and nonfinancial support from Celgene, Amgen, and Merck Sharp & Dohme, during the conduct of the study and personal fees from other companies outside the submitted work.

SOURCE: Cook G et al. Lancet Haematol. 2019 Mar;6(3):e154-66.

A proposed clinical scoring system using readily available laboratory data, rather than complex formulas, can be used to predict risk for overall survival and help with clinical decision making for patients with multiple myeloma who are ineligible for stem cell transplants, the system’s creators claim.

Peter Anderson/ Pathology Education Informational Resource Digital Library/copyright University of Alabama at Birmingham, Department of Pathology

When applied to data from two clinical trials that enrolled patients with transplant-ineligible multiple myeloma, the UK Myeloma Research Alliance Risk Profile (MRP) was shown to accurately group patients into low-, medium- and high-risk categories and was prognostic of overall survival, reported Gordon Cook, PhD, of the University of Leeds, England, and his colleagues.

“The ability of clinical scoring systems, such as that proposed here, to predict whether a patient is likely to stop treatment early because of treatment intolerability, could enable preemptive, upfront dose adjustments in patients with multiple myeloma, preventing toxicity and potentially enabling patients to stay on therapy for longer,” they wrote in the Lancet Haematology.

The investigators used data on 1,852 newly diagnosed patients recruited to the non–intensive treatment pathway of the UK’s National Cancer Research Institute Myeloma XI study (NCRI-XI, ISRCTN49407852) for a training dataset and internal validation dataset, and 520 patients recruited into the Medical Research Council Myeloma IX study (MRC-IX, ISRCTN68454111) for the test dataset.

Patient characteristics, biochemical measurements, and hematological data were plugged into univariate and multivariate models to determine their potential as prognostic variables.

The final model for the test and validation datasets included World Health Organization performance status, the multiple myeloma International Staging System, patient age, and C-reactive protein concentrations.

As noted before, the scoring algorithm groups patients into low-, medium- and high-risk categories, with each of the prognostic variables increasing in severity across the three groups in both clinical trials.

In the NCRI-XI trial, median overall survival for patients in the MRP low-risk group was 60 months, compared with 44 months in the medium-risk group, and 25 months in the high-risk group.

Similarly, in the MRC-IX trial, the respective median overall survival was 49, 34, and 20 months.

The risk groups also were associated with progression-free survival in each trial, although not as robustly as the association with overall survival.

The investigators also found that, the higher the risk group, the greater the likelihood that the median percentage of protocol dose delivered would be lower, and both a decrease in protocol dose delivered and quality of life at baseline were associated with increased risk.

The MRP categories were prognostic in patients treated with various therapeutic regimens and in patients with high-risk cytogenetics.

“None of the risk scoring systems previously developed in myeloma are dynamic, making them unable to accommodate changes in disease-related frailty that might be minimized by effective anti-myeloma therapy. There is therefore scope to improve clinical risk scores by the addition of a suitable frailty biomarker, which is currently still in developmental stages,” Dr. Cook and his colleagues wrote.

The study was funded by the Medical Research Council, Novartis, Schering Health Care, Chugai, Pharmion, Celgene, Ortho Biotech, Cancer Research UK, Celgene, Merck Sharp & Dohme, and Amgen. Dr. Cook reported grants and nonfinancial support from Celgene, Amgen, and Merck Sharp & Dohme, during the conduct of the study and personal fees from other companies outside the submitted work.

SOURCE: Cook G et al. Lancet Haematol. 2019 Mar;6(3):e154-66.

A proposed clinical scoring system using readily available laboratory data, rather than complex formulas, can be used to predict risk for overall survival and help with clinical decision making for patients with multiple myeloma who are ineligible for stem cell transplants, the system’s creators claim.

Peter Anderson/ Pathology Education Informational Resource Digital Library/copyright University of Alabama at Birmingham, Department of Pathology

When applied to data from two clinical trials that enrolled patients with transplant-ineligible multiple myeloma, the UK Myeloma Research Alliance Risk Profile (MRP) was shown to accurately group patients into low-, medium- and high-risk categories and was prognostic of overall survival, reported Gordon Cook, PhD, of the University of Leeds, England, and his colleagues.

“The ability of clinical scoring systems, such as that proposed here, to predict whether a patient is likely to stop treatment early because of treatment intolerability, could enable preemptive, upfront dose adjustments in patients with multiple myeloma, preventing toxicity and potentially enabling patients to stay on therapy for longer,” they wrote in the Lancet Haematology.

The investigators used data on 1,852 newly diagnosed patients recruited to the non–intensive treatment pathway of the UK’s National Cancer Research Institute Myeloma XI study (NCRI-XI, ISRCTN49407852) for a training dataset and internal validation dataset, and 520 patients recruited into the Medical Research Council Myeloma IX study (MRC-IX, ISRCTN68454111) for the test dataset.

Patient characteristics, biochemical measurements, and hematological data were plugged into univariate and multivariate models to determine their potential as prognostic variables.

The final model for the test and validation datasets included World Health Organization performance status, the multiple myeloma International Staging System, patient age, and C-reactive protein concentrations.

As noted before, the scoring algorithm groups patients into low-, medium- and high-risk categories, with each of the prognostic variables increasing in severity across the three groups in both clinical trials.

In the NCRI-XI trial, median overall survival for patients in the MRP low-risk group was 60 months, compared with 44 months in the medium-risk group, and 25 months in the high-risk group.

Similarly, in the MRC-IX trial, the respective median overall survival was 49, 34, and 20 months.

The risk groups also were associated with progression-free survival in each trial, although not as robustly as the association with overall survival.

The investigators also found that, the higher the risk group, the greater the likelihood that the median percentage of protocol dose delivered would be lower, and both a decrease in protocol dose delivered and quality of life at baseline were associated with increased risk.

The MRP categories were prognostic in patients treated with various therapeutic regimens and in patients with high-risk cytogenetics.

“None of the risk scoring systems previously developed in myeloma are dynamic, making them unable to accommodate changes in disease-related frailty that might be minimized by effective anti-myeloma therapy. There is therefore scope to improve clinical risk scores by the addition of a suitable frailty biomarker, which is currently still in developmental stages,” Dr. Cook and his colleagues wrote.

The study was funded by the Medical Research Council, Novartis, Schering Health Care, Chugai, Pharmion, Celgene, Ortho Biotech, Cancer Research UK, Celgene, Merck Sharp & Dohme, and Amgen. Dr. Cook reported grants and nonfinancial support from Celgene, Amgen, and Merck Sharp & Dohme, during the conduct of the study and personal fees from other companies outside the submitted work.

SOURCE: Cook G et al. Lancet Haematol. 2019 Mar;6(3):e154-66.

The Food and Drug Administration has granted accelerated approval for the combination of atezolizumab (Tecentriq) plus nanoparticle albumin–bound paclitaxel (nab-paclitaxel; Abraxane) for the treatment of adults with unresectable locally advanced or metastatic programmed death-ligand 1 (PD-L1)–positive triple-negative breast cancer (TNBC).

This conditional approval is granted to medicines that fill an unmet medical need for serious or life-threatening diseases or conditions, but the FDA may require confirmatory trials to provide verification and description of clinical benefit to allow continued approval.

The approval is based on the phase 3 IMpassion130 trial (NCT02425891), which enrolled 902 patients with unresectable, locally advanced or metastatic TNBC who had not received prior lines of chemo for metastatic disease, according to Genentech.

The multicenter, randomized, double-blind study has been evaluating the drug combination’s efficacy, safety, and pharmacokinetics. Compared with placebo plus nab-paclitaxel, atezolizumab/nab-paclitaxel demonstrated significantly superior progression-free survival (median PFS, 7.4 months vs. 4.8 months; hazard ratio, 0.60; 95% confidence interval, 0.48-0.77; P less than .0001).

The overall survival data for the intention-to-treat population remains immature, but further data will be shared with the FDA in the future, according to Genentech.

No new safety signals were seen in the atezolizumab/nab-paclitaxel arm, and the combination’s safety appeared consistent with the known safety profiles of each medicine individually.

The most common grade 3-4 events (occurring in more than 2% of patients) in the combination arm included low red blood cells, low white blood cells, feeling tired, low blood potassium level, and pneumonia.

The most common side effects (occurring in more than 20% of patients) in the combination arm included hair loss, tingling, nausea, diarrhea, headache, low red blood cells, low white blood cells, and decreased appetite.

Atezolizumab is a monoclonal antibody that binds to the PD-L1 receptor, which could possibly lead to the reactivation of T cells; however, atezolizumab also may interact with other cells in the body. Nab-paclitaxel is an injectable suspension of the common chemotherapy drug.

cpalmer@mdedge.com

The Food and Drug Administration has granted accelerated approval for the combination of atezolizumab (Tecentriq) plus nanoparticle albumin–bound paclitaxel (nab-paclitaxel; Abraxane) for the treatment of adults with unresectable locally advanced or metastatic programmed death-ligand 1 (PD-L1)–positive triple-negative breast cancer (TNBC).

This conditional approval is granted to medicines that fill an unmet medical need for serious or life-threatening diseases or conditions, but the FDA may require confirmatory trials to provide verification and description of clinical benefit to allow continued approval.

The approval is based on the phase 3 IMpassion130 trial (NCT02425891), which enrolled 902 patients with unresectable, locally advanced or metastatic TNBC who had not received prior lines of chemo for metastatic disease, according to Genentech.

The multicenter, randomized, double-blind study has been evaluating the drug combination’s efficacy, safety, and pharmacokinetics. Compared with placebo plus nab-paclitaxel, atezolizumab/nab-paclitaxel demonstrated significantly superior progression-free survival (median PFS, 7.4 months vs. 4.8 months; hazard ratio, 0.60; 95% confidence interval, 0.48-0.77; P less than .0001).

The overall survival data for the intention-to-treat population remains immature, but further data will be shared with the FDA in the future, according to Genentech.

No new safety signals were seen in the atezolizumab/nab-paclitaxel arm, and the combination’s safety appeared consistent with the known safety profiles of each medicine individually.

The most common grade 3-4 events (occurring in more than 2% of patients) in the combination arm included low red blood cells, low white blood cells, feeling tired, low blood potassium level, and pneumonia.

The most common side effects (occurring in more than 20% of patients) in the combination arm included hair loss, tingling, nausea, diarrhea, headache, low red blood cells, low white blood cells, and decreased appetite.

Atezolizumab is a monoclonal antibody that binds to the PD-L1 receptor, which could possibly lead to the reactivation of T cells; however, atezolizumab also may interact with other cells in the body. Nab-paclitaxel is an injectable suspension of the common chemotherapy drug.

cpalmer@mdedge.com

The Food and Drug Administration has granted accelerated approval for the combination of atezolizumab (Tecentriq) plus nanoparticle albumin–bound paclitaxel (nab-paclitaxel; Abraxane) for the treatment of adults with unresectable locally advanced or metastatic programmed death-ligand 1 (PD-L1)–positive triple-negative breast cancer (TNBC).

This conditional approval is granted to medicines that fill an unmet medical need for serious or life-threatening diseases or conditions, but the FDA may require confirmatory trials to provide verification and description of clinical benefit to allow continued approval.

The approval is based on the phase 3 IMpassion130 trial (NCT02425891), which enrolled 902 patients with unresectable, locally advanced or metastatic TNBC who had not received prior lines of chemo for metastatic disease, according to Genentech.

The multicenter, randomized, double-blind study has been evaluating the drug combination’s efficacy, safety, and pharmacokinetics. Compared with placebo plus nab-paclitaxel, atezolizumab/nab-paclitaxel demonstrated significantly superior progression-free survival (median PFS, 7.4 months vs. 4.8 months; hazard ratio, 0.60; 95% confidence interval, 0.48-0.77; P less than .0001).

The overall survival data for the intention-to-treat population remains immature, but further data will be shared with the FDA in the future, according to Genentech.

No new safety signals were seen in the atezolizumab/nab-paclitaxel arm, and the combination’s safety appeared consistent with the known safety profiles of each medicine individually.

The most common grade 3-4 events (occurring in more than 2% of patients) in the combination arm included low red blood cells, low white blood cells, feeling tired, low blood potassium level, and pneumonia.

The most common side effects (occurring in more than 20% of patients) in the combination arm included hair loss, tingling, nausea, diarrhea, headache, low red blood cells, low white blood cells, and decreased appetite.

Atezolizumab is a monoclonal antibody that binds to the PD-L1 receptor, which could possibly lead to the reactivation of T cells; however, atezolizumab also may interact with other cells in the body. Nab-paclitaxel is an injectable suspension of the common chemotherapy drug.

cpalmer@mdedge.com

SAN FRANCISCO – For patients with advanced non–small cell lung cancer (NSCLC) who previously had disease control with the checkpoint inhibitor nivolumab (Opdivo), second-line nivolumab at a higher dose every 4 weeks appeared to be comparable in efficacy and safety with standard-dose nivolumab every 2 weeks.

The key word in that last sentence is “appeared,” because the Checkmate 384 trial that was designed to show noninferiority of the every-4-weeks regimen lacked the statistical muscle to get the job done, reported Edward B. Garon, MD, from the University of California, Los Angeles.

“In many respects, extending the dosing frequency of nivolumab fulfills some of the promise of immunotherapy: The idea that we would be able to decrease the medicalization of the lives of our patients. For some people this would lead to them being able to resume a more normal work schedule, and for other people it would allow them to do things for fun, like travel on trips that would take longer than a couple of weeks,” he said at the American Society of Clinical Oncology (ASCO) – Society for Immunotherapy of Cancer (SITC): Clinical Immuno-Oncology Symposium.

However, because of difficulties in recruitment, the investigators had to stop enrollment early and settle for a sample size of 363 patients, instead of the 600 planned that would be necessary to meet a 10% noninferiority margin and one-sided 95% confidence interval. Thus, the trial analysis can only be reported as descriptive rather than definitive, Dr. Garon acknowledged.

Nivolumab is approved at a fixed dose of 240 mg every 2 weeks for the treatment of multiple tumor types in several different nations, and in the United States and Canada it is approved at a dose of 480 mg every 4 weeks for the treatment of NSCLC.

The CheckMate 384 study enrolled patients with advanced or metastatic NSCLC who had received 3 mg/kg or 240 mg of nivolumab every 2 weeks for up to 1 year. The patients had to have had relatively good performance status (Eastern Cooperative Oncology Group 0-2) and two consecutive assessments of either complete response, partial response, or stable disease.

The patients were stratified by tumor histology (squamous or nonsquamous) and response to prior nivolumab therapy at randomization, and were then randomized to receive nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks until disease progression or unacceptable toxicity for up to 2 years.

Dr. Garon presented an interim analysis including data on 329 of the 363 patients; the final analysis will occur after all patients have had a minimum of 12 months of follow-up. Here, he reported on 6-month progression-free survival, a coprimary endpoint with 12-month PFS.

After a median follow-up of 9.5 months in the Q4-week group and 10.2 months in the Q2-week group, the 6-month PFS rates were identical between the two dosing strategies, at 72%. The median PFS was 12.1 months and 12.2 months, respectively.

“Although the study is no longer formally powered to show noninferiority, there’s certainly nothing in these curves that makes me concerned that this 480 mg every-4-week dose would be inferior,” Dr. Garon said.

There was a slightly higher rate of treatment-related adverse events of any grade in the lower, more frequent dose group: 48% in the Q4-week versus 61% in the Q2-week arm. The respective rates of grade 3 or 4 adverse events were 8% and 12%. Rates of serious adverse events and events leading to treatment discontinuation were similar between the group; there were no treatment-related deaths.

The investigators hypothesize that the higher rate of overall events in the lower-dose group may be attributable to more frequent visits and more opportunities to report adverse events, Dr. Garon said.

“Overall, the clinical data are in agreement with the pharmacokinetic modeling and give further evidence for this 480 mg every 4 week nivolumab dosing option,” he concluded.

The study was supported by Bristol-Myers Squibb. Dr. Garon reported receiving research support from Bristol-Myers Squibb and others and consulting fees from Dracen Pharmaceuticals.

SOURCE: Garon EB et al. ASCO-SITC, Abstract 100.

SAN FRANCISCO – For patients with advanced non–small cell lung cancer (NSCLC) who previously had disease control with the checkpoint inhibitor nivolumab (Opdivo), second-line nivolumab at a higher dose every 4 weeks appeared to be comparable in efficacy and safety with standard-dose nivolumab every 2 weeks.

The key word in that last sentence is “appeared,” because the Checkmate 384 trial that was designed to show noninferiority of the every-4-weeks regimen lacked the statistical muscle to get the job done, reported Edward B. Garon, MD, from the University of California, Los Angeles.

“In many respects, extending the dosing frequency of nivolumab fulfills some of the promise of immunotherapy: The idea that we would be able to decrease the medicalization of the lives of our patients. For some people this would lead to them being able to resume a more normal work schedule, and for other people it would allow them to do things for fun, like travel on trips that would take longer than a couple of weeks,” he said at the American Society of Clinical Oncology (ASCO) – Society for Immunotherapy of Cancer (SITC): Clinical Immuno-Oncology Symposium.

However, because of difficulties in recruitment, the investigators had to stop enrollment early and settle for a sample size of 363 patients, instead of the 600 planned that would be necessary to meet a 10% noninferiority margin and one-sided 95% confidence interval. Thus, the trial analysis can only be reported as descriptive rather than definitive, Dr. Garon acknowledged.

Nivolumab is approved at a fixed dose of 240 mg every 2 weeks for the treatment of multiple tumor types in several different nations, and in the United States and Canada it is approved at a dose of 480 mg every 4 weeks for the treatment of NSCLC.

The CheckMate 384 study enrolled patients with advanced or metastatic NSCLC who had received 3 mg/kg or 240 mg of nivolumab every 2 weeks for up to 1 year. The patients had to have had relatively good performance status (Eastern Cooperative Oncology Group 0-2) and two consecutive assessments of either complete response, partial response, or stable disease.

The patients were stratified by tumor histology (squamous or nonsquamous) and response to prior nivolumab therapy at randomization, and were then randomized to receive nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks until disease progression or unacceptable toxicity for up to 2 years.

Dr. Garon presented an interim analysis including data on 329 of the 363 patients; the final analysis will occur after all patients have had a minimum of 12 months of follow-up. Here, he reported on 6-month progression-free survival, a coprimary endpoint with 12-month PFS.

After a median follow-up of 9.5 months in the Q4-week group and 10.2 months in the Q2-week group, the 6-month PFS rates were identical between the two dosing strategies, at 72%. The median PFS was 12.1 months and 12.2 months, respectively.

“Although the study is no longer formally powered to show noninferiority, there’s certainly nothing in these curves that makes me concerned that this 480 mg every-4-week dose would be inferior,” Dr. Garon said.

There was a slightly higher rate of treatment-related adverse events of any grade in the lower, more frequent dose group: 48% in the Q4-week versus 61% in the Q2-week arm. The respective rates of grade 3 or 4 adverse events were 8% and 12%. Rates of serious adverse events and events leading to treatment discontinuation were similar between the group; there were no treatment-related deaths.

The investigators hypothesize that the higher rate of overall events in the lower-dose group may be attributable to more frequent visits and more opportunities to report adverse events, Dr. Garon said.

“Overall, the clinical data are in agreement with the pharmacokinetic modeling and give further evidence for this 480 mg every 4 week nivolumab dosing option,” he concluded.

The study was supported by Bristol-Myers Squibb. Dr. Garon reported receiving research support from Bristol-Myers Squibb and others and consulting fees from Dracen Pharmaceuticals.

SOURCE: Garon EB et al. ASCO-SITC, Abstract 100.

SAN FRANCISCO – For patients with advanced non–small cell lung cancer (NSCLC) who previously had disease control with the checkpoint inhibitor nivolumab (Opdivo), second-line nivolumab at a higher dose every 4 weeks appeared to be comparable in efficacy and safety with standard-dose nivolumab every 2 weeks.

The key word in that last sentence is “appeared,” because the Checkmate 384 trial that was designed to show noninferiority of the every-4-weeks regimen lacked the statistical muscle to get the job done, reported Edward B. Garon, MD, from the University of California, Los Angeles.

“In many respects, extending the dosing frequency of nivolumab fulfills some of the promise of immunotherapy: The idea that we would be able to decrease the medicalization of the lives of our patients. For some people this would lead to them being able to resume a more normal work schedule, and for other people it would allow them to do things for fun, like travel on trips that would take longer than a couple of weeks,” he said at the American Society of Clinical Oncology (ASCO) – Society for Immunotherapy of Cancer (SITC): Clinical Immuno-Oncology Symposium.

However, because of difficulties in recruitment, the investigators had to stop enrollment early and settle for a sample size of 363 patients, instead of the 600 planned that would be necessary to meet a 10% noninferiority margin and one-sided 95% confidence interval. Thus, the trial analysis can only be reported as descriptive rather than definitive, Dr. Garon acknowledged.

Nivolumab is approved at a fixed dose of 240 mg every 2 weeks for the treatment of multiple tumor types in several different nations, and in the United States and Canada it is approved at a dose of 480 mg every 4 weeks for the treatment of NSCLC.

The CheckMate 384 study enrolled patients with advanced or metastatic NSCLC who had received 3 mg/kg or 240 mg of nivolumab every 2 weeks for up to 1 year. The patients had to have had relatively good performance status (Eastern Cooperative Oncology Group 0-2) and two consecutive assessments of either complete response, partial response, or stable disease.

The patients were stratified by tumor histology (squamous or nonsquamous) and response to prior nivolumab therapy at randomization, and were then randomized to receive nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks until disease progression or unacceptable toxicity for up to 2 years.

Dr. Garon presented an interim analysis including data on 329 of the 363 patients; the final analysis will occur after all patients have had a minimum of 12 months of follow-up. Here, he reported on 6-month progression-free survival, a coprimary endpoint with 12-month PFS.

After a median follow-up of 9.5 months in the Q4-week group and 10.2 months in the Q2-week group, the 6-month PFS rates were identical between the two dosing strategies, at 72%. The median PFS was 12.1 months and 12.2 months, respectively.

“Although the study is no longer formally powered to show noninferiority, there’s certainly nothing in these curves that makes me concerned that this 480 mg every-4-week dose would be inferior,” Dr. Garon said.

There was a slightly higher rate of treatment-related adverse events of any grade in the lower, more frequent dose group: 48% in the Q4-week versus 61% in the Q2-week arm. The respective rates of grade 3 or 4 adverse events were 8% and 12%. Rates of serious adverse events and events leading to treatment discontinuation were similar between the group; there were no treatment-related deaths.

The investigators hypothesize that the higher rate of overall events in the lower-dose group may be attributable to more frequent visits and more opportunities to report adverse events, Dr. Garon said.

“Overall, the clinical data are in agreement with the pharmacokinetic modeling and give further evidence for this 480 mg every 4 week nivolumab dosing option,” he concluded.

The study was supported by Bristol-Myers Squibb. Dr. Garon reported receiving research support from Bristol-Myers Squibb and others and consulting fees from Dracen Pharmaceuticals.

SOURCE: Garon EB et al. ASCO-SITC, Abstract 100.

In this episode, Alok Khorana, MD, of the Cleveland Clinic, joins David H. Henry, MD, to discuss results from the CASSINI trial and what it means for anticoagulation in cancer patients.
And Ilana Yurkiewicz, MD, begins part 1 of her look at informed consent. Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University and is also a columnist for Hematology News. More from Dr. Yurkiewicz here.
Subscribe to Blood & Cancer here:
Apple Podcasts

Google Podcasts

In this episode, Alok Khorana, MD, of the Cleveland Clinic, joins David H. Henry, MD, to discuss results from the CASSINI trial and what it means for anticoagulation in cancer patients.
And Ilana Yurkiewicz, MD, begins part 1 of her look at informed consent. Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University and is also a columnist for Hematology News. More from Dr. Yurkiewicz here.
Subscribe to Blood & Cancer here:
Apple Podcasts

Google Podcasts

In this episode, Alok Khorana, MD, of the Cleveland Clinic, joins David H. Henry, MD, to discuss results from the CASSINI trial and what it means for anticoagulation in cancer patients.
And Ilana Yurkiewicz, MD, begins part 1 of her look at informed consent. Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University and is also a columnist for Hematology News. More from Dr. Yurkiewicz here.
Subscribe to Blood & Cancer here:
Apple Podcasts

Google Podcasts

HOUSTON – Lentiviral gene therapy appears safe and was potentially effective in a rare primary immunodeficiency disease known as X-linked chronic granulomatous disease, said Donald B. Kohn, MD, of the University of California, Los Angeles.

Seven of nine patients treated were “alive and well” at 12 months’ follow-up after receiving lentiviral vector transduced CD34+ cells, Dr. Kohn reported in a late-breaking clinical trial session at the Transplantation & Cellular Therapy Meetings.

Most patients were able to discontinue antibiotic prophylaxis for this disease, which is associated with severe, recurrent, and prolonged life-threatening infections, he said.

Results of the small study provide “proof of concept” for use of the gene therapy in the disease, though additional studies are needed to formally assess the clinical safety and efficacy of the approach, he said.

The estimated incidence of chronic granulomatous disease is 1 in 200,000 births in the United States, and the X-linked form is most common, occurring in about 60% of patients, Dr. Kohn told attendees of the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Most of these patients are treated with antibacterial or antifungal prophylaxis. While allogeneic hematopoietic stem cell transplantation is also an option, according to Dr. Kohn, the approach is limited by a lack of matched donors and graft-versus-host disease.

Dr. Kohn reported results for nine patients in the United States and the United Kingdom who were treated with the same G1XCGD lentiviral vector. The patients, who ranged in age from 2 to 27 years, underwent CD34+ cell mobilization or bone marrow isolation, transduction with the lentiviral vector, busulfan conditioning, and autologous transplantation.

All patients had confirmed X-linked chronic granulomatous disease, and had had at least one severe infection or inflammatory complication requiring hospitalization.

There were no infusion-related adverse events, and one serious adverse event, which was an inflammatory syndrome that resolved with steroids. Two patients died from complications unrelated to gene therapy, Dr. Kohn reported.

“The other patients are basically doing quite well,” he said.

Of the seven patients alive at the 12-month follow up, six were reported as “clinically well” and off antibiotic prophylaxis, according to Dr. Kohn, while the seventh patient was clinically well and receiving antimicrobial support.

Dr. Kohn is a scientific advisory board member for Orchard Therapeutics, which licensed the lentiviral gene therapy for X-CGD discussed in his presentation. He is also an inventor of intellectual property related to the therapy that UCLA has licensed to Orchard.

At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

SOURCE: Kohn DB et al. TCT 2019, Abstract LBA1.

HOUSTON – Lentiviral gene therapy appears safe and was potentially effective in a rare primary immunodeficiency disease known as X-linked chronic granulomatous disease, said Donald B. Kohn, MD, of the University of California, Los Angeles.

Seven of nine patients treated were “alive and well” at 12 months’ follow-up after receiving lentiviral vector transduced CD34+ cells, Dr. Kohn reported in a late-breaking clinical trial session at the Transplantation & Cellular Therapy Meetings.

Most patients were able to discontinue antibiotic prophylaxis for this disease, which is associated with severe, recurrent, and prolonged life-threatening infections, he said.

Results of the small study provide “proof of concept” for use of the gene therapy in the disease, though additional studies are needed to formally assess the clinical safety and efficacy of the approach, he said.

The estimated incidence of chronic granulomatous disease is 1 in 200,000 births in the United States, and the X-linked form is most common, occurring in about 60% of patients, Dr. Kohn told attendees of the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Most of these patients are treated with antibacterial or antifungal prophylaxis. While allogeneic hematopoietic stem cell transplantation is also an option, according to Dr. Kohn, the approach is limited by a lack of matched donors and graft-versus-host disease.

Dr. Kohn reported results for nine patients in the United States and the United Kingdom who were treated with the same G1XCGD lentiviral vector. The patients, who ranged in age from 2 to 27 years, underwent CD34+ cell mobilization or bone marrow isolation, transduction with the lentiviral vector, busulfan conditioning, and autologous transplantation.

All patients had confirmed X-linked chronic granulomatous disease, and had had at least one severe infection or inflammatory complication requiring hospitalization.

There were no infusion-related adverse events, and one serious adverse event, which was an inflammatory syndrome that resolved with steroids. Two patients died from complications unrelated to gene therapy, Dr. Kohn reported.

“The other patients are basically doing quite well,” he said.

Of the seven patients alive at the 12-month follow up, six were reported as “clinically well” and off antibiotic prophylaxis, according to Dr. Kohn, while the seventh patient was clinically well and receiving antimicrobial support.

Dr. Kohn is a scientific advisory board member for Orchard Therapeutics, which licensed the lentiviral gene therapy for X-CGD discussed in his presentation. He is also an inventor of intellectual property related to the therapy that UCLA has licensed to Orchard.

At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

SOURCE: Kohn DB et al. TCT 2019, Abstract LBA1.

HOUSTON – Lentiviral gene therapy appears safe and was potentially effective in a rare primary immunodeficiency disease known as X-linked chronic granulomatous disease, said Donald B. Kohn, MD, of the University of California, Los Angeles.

Seven of nine patients treated were “alive and well” at 12 months’ follow-up after receiving lentiviral vector transduced CD34+ cells, Dr. Kohn reported in a late-breaking clinical trial session at the Transplantation & Cellular Therapy Meetings.

Most patients were able to discontinue antibiotic prophylaxis for this disease, which is associated with severe, recurrent, and prolonged life-threatening infections, he said.

Results of the small study provide “proof of concept” for use of the gene therapy in the disease, though additional studies are needed to formally assess the clinical safety and efficacy of the approach, he said.

The estimated incidence of chronic granulomatous disease is 1 in 200,000 births in the United States, and the X-linked form is most common, occurring in about 60% of patients, Dr. Kohn told attendees of the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Most of these patients are treated with antibacterial or antifungal prophylaxis. While allogeneic hematopoietic stem cell transplantation is also an option, according to Dr. Kohn, the approach is limited by a lack of matched donors and graft-versus-host disease.

Dr. Kohn reported results for nine patients in the United States and the United Kingdom who were treated with the same G1XCGD lentiviral vector. The patients, who ranged in age from 2 to 27 years, underwent CD34+ cell mobilization or bone marrow isolation, transduction with the lentiviral vector, busulfan conditioning, and autologous transplantation.

All patients had confirmed X-linked chronic granulomatous disease, and had had at least one severe infection or inflammatory complication requiring hospitalization.

There were no infusion-related adverse events, and one serious adverse event, which was an inflammatory syndrome that resolved with steroids. Two patients died from complications unrelated to gene therapy, Dr. Kohn reported.

“The other patients are basically doing quite well,” he said.

Of the seven patients alive at the 12-month follow up, six were reported as “clinically well” and off antibiotic prophylaxis, according to Dr. Kohn, while the seventh patient was clinically well and receiving antimicrobial support.

Dr. Kohn is a scientific advisory board member for Orchard Therapeutics, which licensed the lentiviral gene therapy for X-CGD discussed in his presentation. He is also an inventor of intellectual property related to the therapy that UCLA has licensed to Orchard.

At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

SOURCE: Kohn DB et al. TCT 2019, Abstract LBA1.

Patients who test positive on a fecal immunochemical test (FIT), even after a recent colonoscopy, should be offered a repeat colonoscopy. That is the conclusion following a review of 2,228 subjects who were FIT positive, which revealed a greater risk of colorectal cancer (CRC) and advanced colo-rectal neoplasia (ACRN) the longer the gap since the last colonoscopy. The findings support the recommendations of the U.S. Multi-Society Task Force on CRC Screening to offer repeat colonoscopies to FIT-positive patients, even if they recently underwent a colonoscopy.

pixologicstudio/Thinkstock

That recommendation was based on low-quality supporting evidence, and there is currently little agreement about whether annual FIT should be performed along with colonoscopy.

The researchers set out to detect the frequency of CRC and ACRN among patients with a positive FIT test. They analyzed data from the National Cancer Screening Program in Korea, which offers an annual FIT for adults aged 50 years and older as an initial screening, followed by a colonoscopy in case of a positive result.

The researchers analyzed data from 52,376 individuals who underwent FIT at a single center in Korea during January 2013–July 2017. They excluded patients with a history of CRC or colorectal surgery, inflammatory bowel disease, or poor bowel preparation.

FIT-positive and FIT-negative patients were divided into three groups based on the length of time since their last colonoscopy: less than 3 years, 3-10 years, or more than 10 years or no colonoscopy.

Compared with FIT-negative subjects, FIT-positive individuals were more likely to be diagnosed with any colorectal neoplasia (61.3% vs. 51.8%; P less than .001), ACRN (20.0% vs. 10.3%; P less than .001), and CRC (5.0% vs. 1.9%; P less than .001).

A total of 6% of subjects had a positive FIT result, and data from 2,228 were analyzed after exclusions. They were compared with 6,135 participants who had negative FIT results but underwent a colonoscopy.

Of patients with a positive FIT result, 23.1% had a colonoscopy less than 3 years before, 19.2% had one 3-10 years prior, and 57.8% had a colonoscopy more than 10 years earlier or had never had one.

March is Colorectal Cancer Awareness Month. AGA is here to help with patient education materials and a new video series. Visit http://crcawareness.gastro.org/ to access all the resources and share on your practice website and social media channels.

SOURCE: Kim NH et al. Gastrointest Endosc. 2019 Jan 23. doi: 10.1016/j.gie.2019.01.012.

Patients who test positive on a fecal immunochemical test (FIT), even after a recent colonoscopy, should be offered a repeat colonoscopy. That is the conclusion following a review of 2,228 subjects who were FIT positive, which revealed a greater risk of colorectal cancer (CRC) and advanced colo-rectal neoplasia (ACRN) the longer the gap since the last colonoscopy. The findings support the recommendations of the U.S. Multi-Society Task Force on CRC Screening to offer repeat colonoscopies to FIT-positive patients, even if they recently underwent a colonoscopy.

pixologicstudio/Thinkstock

That recommendation was based on low-quality supporting evidence, and there is currently little agreement about whether annual FIT should be performed along with colonoscopy.

The researchers set out to detect the frequency of CRC and ACRN among patients with a positive FIT test. They analyzed data from the National Cancer Screening Program in Korea, which offers an annual FIT for adults aged 50 years and older as an initial screening, followed by a colonoscopy in case of a positive result.

The researchers analyzed data from 52,376 individuals who underwent FIT at a single center in Korea during January 2013–July 2017. They excluded patients with a history of CRC or colorectal surgery, inflammatory bowel disease, or poor bowel preparation.

FIT-positive and FIT-negative patients were divided into three groups based on the length of time since their last colonoscopy: less than 3 years, 3-10 years, or more than 10 years or no colonoscopy.

Compared with FIT-negative subjects, FIT-positive individuals were more likely to be diagnosed with any colorectal neoplasia (61.3% vs. 51.8%; P less than .001), ACRN (20.0% vs. 10.3%; P less than .001), and CRC (5.0% vs. 1.9%; P less than .001).

A total of 6% of subjects had a positive FIT result, and data from 2,228 were analyzed after exclusions. They were compared with 6,135 participants who had negative FIT results but underwent a colonoscopy.

Of patients with a positive FIT result, 23.1% had a colonoscopy less than 3 years before, 19.2% had one 3-10 years prior, and 57.8% had a colonoscopy more than 10 years earlier or had never had one.

March is Colorectal Cancer Awareness Month. AGA is here to help with patient education materials and a new video series. Visit http://crcawareness.gastro.org/ to access all the resources and share on your practice website and social media channels.

SOURCE: Kim NH et al. Gastrointest Endosc. 2019 Jan 23. doi: 10.1016/j.gie.2019.01.012.

Patients who test positive on a fecal immunochemical test (FIT), even after a recent colonoscopy, should be offered a repeat colonoscopy. That is the conclusion following a review of 2,228 subjects who were FIT positive, which revealed a greater risk of colorectal cancer (CRC) and advanced colo-rectal neoplasia (ACRN) the longer the gap since the last colonoscopy. The findings support the recommendations of the U.S. Multi-Society Task Force on CRC Screening to offer repeat colonoscopies to FIT-positive patients, even if they recently underwent a colonoscopy.

pixologicstudio/Thinkstock

That recommendation was based on low-quality supporting evidence, and there is currently little agreement about whether annual FIT should be performed along with colonoscopy.

The researchers set out to detect the frequency of CRC and ACRN among patients with a positive FIT test. They analyzed data from the National Cancer Screening Program in Korea, which offers an annual FIT for adults aged 50 years and older as an initial screening, followed by a colonoscopy in case of a positive result.

The researchers analyzed data from 52,376 individuals who underwent FIT at a single center in Korea during January 2013–July 2017. They excluded patients with a history of CRC or colorectal surgery, inflammatory bowel disease, or poor bowel preparation.

FIT-positive and FIT-negative patients were divided into three groups based on the length of time since their last colonoscopy: less than 3 years, 3-10 years, or more than 10 years or no colonoscopy.

Compared with FIT-negative subjects, FIT-positive individuals were more likely to be diagnosed with any colorectal neoplasia (61.3% vs. 51.8%; P less than .001), ACRN (20.0% vs. 10.3%; P less than .001), and CRC (5.0% vs. 1.9%; P less than .001).

A total of 6% of subjects had a positive FIT result, and data from 2,228 were analyzed after exclusions. They were compared with 6,135 participants who had negative FIT results but underwent a colonoscopy.

Of patients with a positive FIT result, 23.1% had a colonoscopy less than 3 years before, 19.2% had one 3-10 years prior, and 57.8% had a colonoscopy more than 10 years earlier or had never had one.

March is Colorectal Cancer Awareness Month. AGA is here to help with patient education materials and a new video series. Visit http://crcawareness.gastro.org/ to access all the resources and share on your practice website and social media channels.

SOURCE: Kim NH et al. Gastrointest Endosc. 2019 Jan 23. doi: 10.1016/j.gie.2019.01.012.