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Nivolumab may provide a benefit for a small group of patients with diffuse large B-cell lymphoma (DLBCL) who have failed a transplant or are ineligible for one, according to researchers.
Nivolumab produced a response in 10 of 121 DLBCL patients studied. Three patients achieved a complete response (CR) lasting 11 months or more.
Why this small group responded to nivolumab isn’t clear, according to Stephen M. Ansell, MD, PhD, of the Mayo Clinic in Rochester, Minn., and his colleagues.
Some responders did have 9p24.1 alterations, but others did not. None of the responders had tumor cells positive for programmed death–ligand 1 (PD-L1), and only one responder had detectable PD-L2 expression in malignant cells.
Dr. Ansell and his colleagues described these findings in the Journal of Clinical Oncology.
The researchers evaluated nivolumab in a phase 2 trial (NCT02038933) of patients with relapsed/refractory DLBCL. Of the 121 patients, 87 had failed autologous hematopoietic stem cell transplant (HSCT) and 34 were ineligible for autologous HSCT. The patients received nivolumab at 3 mg/kg every 2 weeks until disease progression, unacceptable toxicity, or study withdrawal.
HSCT failures
The patients who had failed HSCT had a median age of 62 years (range, 24-75 years). They had received a median of three prior systemic therapies (range, 1-11), and 28% were refractory to their most recent therapy.
About 40% of patients had germinal center B-cell–like (GCB) DLBCL, 32% had non-GCB disease, and data on disease subtype were missing for the rest of the group.
The patients received a median of four nivolumab doses (range, 1-44) and were followed for a median of 9 months (range, 0.1-25 months).
Nine patients (10%) achieved a response, and the median duration of response was 11 months. Responses occurred in patients with GCB and non-GCB DLBCL.
Three patients achieved a CR. Two of them were still on treatment and in CR at the data cutoff. Their responses had lasted 11 months and 14 months, respectively. The third complete responder did not progress on nivolumab but developed myelodysplastic syndrome, which was unrelated to the drug, and died.
Among all patients who had failed HSCT, the median progression-free survival was 1.9 months, and the median overall survival was 12.2 months.
Seven patients in this group were still receiving nivolumab at the data cutoff. Two of them were in CR, two had a partial response, and three had stable disease.
HSCT-ineligible group
The patients who were ineligible for HSCT had a median age of 68 years (range, 28-86 years). They had received a median of three prior systemic therapies (range, 1-7), and 59% were refractory to their most recent therapy.
About 56% of these patients had GCB DLBCL, 18% had non-GCB disease, and data on subtype were missing for the rest of the group.
The patients received a median of three nivolumab doses (range, 1-22) and were followed for a median of 6 months (range, 0.2-24 months). One patient (3%) achieved a partial response, which lasted 8.3 months.
The median progression-free survival in this group was 1.4 months, and the median overall survival was 5.8 months.
None of the patients in this group were still taking nivolumab at the data cutoff.
Biomarkers of response
Dr. Ansell and his colleagues were able to look for 9p24.1 alterations in archival tumor biopsy specimens from 74 patients. The team reported that 9p24.1 alterations were “infrequent,” but they were found in some responders.
Among the three complete responders, one patient had high-level 9p24.1 amplification, one had normal 9p24.1 copy number, and one did not have a biopsy available.
Among the seven patients who achieved a partial response, five had biopsy specimens. Three patients had low-level polysomy, one had copy gain, and one patient had normal 9p24.1.
None of the responders had PD-L1 expression in their tumor cells, but one complete responder had PD-L2–positive malignant cells.
Dr. Ansell and his colleagues wrote that the “biologic basis for response in the other two [complete responders] is unclear,” and the researchers were unable to assess associations between response and c-myc expression or double-hit lymphoma.
Safety
Of all 121 patients, 62% had a treatment-related adverse event (AE) and 24% had a grade 3/4–related AE.
The most common related AEs of any grade were nausea (17%), fatigue (17%), diarrhea (10%), neutropenia (7%), thrombocytopenia (6%), decreased appetite (6%), lipase increase (5%), rash (5%), and pyrexia (5%).
Four patients (3%) stopped taking nivolumab because of treatment-related AEs, including neutropenia, thrombocytopenia, diarrhea, pancreatitis, lipase increase, and psoriasiform dermatitis. There were no fatal treatment-related AEs.
This research was supported by Bristol-Myers Squibb and other groups. The study authors reported relationships with Bristol-Myers Squibb and other companies.
SOURCE: Ansell SM et al. J Clin Oncol. 2019 Jan 8. doi: 10.1200/JCO.18.00766.
Nivolumab may provide a benefit for a small group of patients with diffuse large B-cell lymphoma (DLBCL) who have failed a transplant or are ineligible for one, according to researchers.
Nivolumab produced a response in 10 of 121 DLBCL patients studied. Three patients achieved a complete response (CR) lasting 11 months or more.
Why this small group responded to nivolumab isn’t clear, according to Stephen M. Ansell, MD, PhD, of the Mayo Clinic in Rochester, Minn., and his colleagues.
Some responders did have 9p24.1 alterations, but others did not. None of the responders had tumor cells positive for programmed death–ligand 1 (PD-L1), and only one responder had detectable PD-L2 expression in malignant cells.
Dr. Ansell and his colleagues described these findings in the Journal of Clinical Oncology.
The researchers evaluated nivolumab in a phase 2 trial (NCT02038933) of patients with relapsed/refractory DLBCL. Of the 121 patients, 87 had failed autologous hematopoietic stem cell transplant (HSCT) and 34 were ineligible for autologous HSCT. The patients received nivolumab at 3 mg/kg every 2 weeks until disease progression, unacceptable toxicity, or study withdrawal.
HSCT failures
The patients who had failed HSCT had a median age of 62 years (range, 24-75 years). They had received a median of three prior systemic therapies (range, 1-11), and 28% were refractory to their most recent therapy.
About 40% of patients had germinal center B-cell–like (GCB) DLBCL, 32% had non-GCB disease, and data on disease subtype were missing for the rest of the group.
The patients received a median of four nivolumab doses (range, 1-44) and were followed for a median of 9 months (range, 0.1-25 months).
Nine patients (10%) achieved a response, and the median duration of response was 11 months. Responses occurred in patients with GCB and non-GCB DLBCL.
Three patients achieved a CR. Two of them were still on treatment and in CR at the data cutoff. Their responses had lasted 11 months and 14 months, respectively. The third complete responder did not progress on nivolumab but developed myelodysplastic syndrome, which was unrelated to the drug, and died.
Among all patients who had failed HSCT, the median progression-free survival was 1.9 months, and the median overall survival was 12.2 months.
Seven patients in this group were still receiving nivolumab at the data cutoff. Two of them were in CR, two had a partial response, and three had stable disease.
HSCT-ineligible group
The patients who were ineligible for HSCT had a median age of 68 years (range, 28-86 years). They had received a median of three prior systemic therapies (range, 1-7), and 59% were refractory to their most recent therapy.
About 56% of these patients had GCB DLBCL, 18% had non-GCB disease, and data on subtype were missing for the rest of the group.
The patients received a median of three nivolumab doses (range, 1-22) and were followed for a median of 6 months (range, 0.2-24 months). One patient (3%) achieved a partial response, which lasted 8.3 months.
The median progression-free survival in this group was 1.4 months, and the median overall survival was 5.8 months.
None of the patients in this group were still taking nivolumab at the data cutoff.
Biomarkers of response
Dr. Ansell and his colleagues were able to look for 9p24.1 alterations in archival tumor biopsy specimens from 74 patients. The team reported that 9p24.1 alterations were “infrequent,” but they were found in some responders.
Among the three complete responders, one patient had high-level 9p24.1 amplification, one had normal 9p24.1 copy number, and one did not have a biopsy available.
Among the seven patients who achieved a partial response, five had biopsy specimens. Three patients had low-level polysomy, one had copy gain, and one patient had normal 9p24.1.
None of the responders had PD-L1 expression in their tumor cells, but one complete responder had PD-L2–positive malignant cells.
Dr. Ansell and his colleagues wrote that the “biologic basis for response in the other two [complete responders] is unclear,” and the researchers were unable to assess associations between response and c-myc expression or double-hit lymphoma.
Safety
Of all 121 patients, 62% had a treatment-related adverse event (AE) and 24% had a grade 3/4–related AE.
The most common related AEs of any grade were nausea (17%), fatigue (17%), diarrhea (10%), neutropenia (7%), thrombocytopenia (6%), decreased appetite (6%), lipase increase (5%), rash (5%), and pyrexia (5%).
Four patients (3%) stopped taking nivolumab because of treatment-related AEs, including neutropenia, thrombocytopenia, diarrhea, pancreatitis, lipase increase, and psoriasiform dermatitis. There were no fatal treatment-related AEs.
This research was supported by Bristol-Myers Squibb and other groups. The study authors reported relationships with Bristol-Myers Squibb and other companies.
SOURCE: Ansell SM et al. J Clin Oncol. 2019 Jan 8. doi: 10.1200/JCO.18.00766.
Nivolumab may provide a benefit for a small group of patients with diffuse large B-cell lymphoma (DLBCL) who have failed a transplant or are ineligible for one, according to researchers.
Nivolumab produced a response in 10 of 121 DLBCL patients studied. Three patients achieved a complete response (CR) lasting 11 months or more.
Why this small group responded to nivolumab isn’t clear, according to Stephen M. Ansell, MD, PhD, of the Mayo Clinic in Rochester, Minn., and his colleagues.
Some responders did have 9p24.1 alterations, but others did not. None of the responders had tumor cells positive for programmed death–ligand 1 (PD-L1), and only one responder had detectable PD-L2 expression in malignant cells.
Dr. Ansell and his colleagues described these findings in the Journal of Clinical Oncology.
The researchers evaluated nivolumab in a phase 2 trial (NCT02038933) of patients with relapsed/refractory DLBCL. Of the 121 patients, 87 had failed autologous hematopoietic stem cell transplant (HSCT) and 34 were ineligible for autologous HSCT. The patients received nivolumab at 3 mg/kg every 2 weeks until disease progression, unacceptable toxicity, or study withdrawal.
HSCT failures
The patients who had failed HSCT had a median age of 62 years (range, 24-75 years). They had received a median of three prior systemic therapies (range, 1-11), and 28% were refractory to their most recent therapy.
About 40% of patients had germinal center B-cell–like (GCB) DLBCL, 32% had non-GCB disease, and data on disease subtype were missing for the rest of the group.
The patients received a median of four nivolumab doses (range, 1-44) and were followed for a median of 9 months (range, 0.1-25 months).
Nine patients (10%) achieved a response, and the median duration of response was 11 months. Responses occurred in patients with GCB and non-GCB DLBCL.
Three patients achieved a CR. Two of them were still on treatment and in CR at the data cutoff. Their responses had lasted 11 months and 14 months, respectively. The third complete responder did not progress on nivolumab but developed myelodysplastic syndrome, which was unrelated to the drug, and died.
Among all patients who had failed HSCT, the median progression-free survival was 1.9 months, and the median overall survival was 12.2 months.
Seven patients in this group were still receiving nivolumab at the data cutoff. Two of them were in CR, two had a partial response, and three had stable disease.
HSCT-ineligible group
The patients who were ineligible for HSCT had a median age of 68 years (range, 28-86 years). They had received a median of three prior systemic therapies (range, 1-7), and 59% were refractory to their most recent therapy.
About 56% of these patients had GCB DLBCL, 18% had non-GCB disease, and data on subtype were missing for the rest of the group.
The patients received a median of three nivolumab doses (range, 1-22) and were followed for a median of 6 months (range, 0.2-24 months). One patient (3%) achieved a partial response, which lasted 8.3 months.
The median progression-free survival in this group was 1.4 months, and the median overall survival was 5.8 months.
None of the patients in this group were still taking nivolumab at the data cutoff.
Biomarkers of response
Dr. Ansell and his colleagues were able to look for 9p24.1 alterations in archival tumor biopsy specimens from 74 patients. The team reported that 9p24.1 alterations were “infrequent,” but they were found in some responders.
Among the three complete responders, one patient had high-level 9p24.1 amplification, one had normal 9p24.1 copy number, and one did not have a biopsy available.
Among the seven patients who achieved a partial response, five had biopsy specimens. Three patients had low-level polysomy, one had copy gain, and one patient had normal 9p24.1.
None of the responders had PD-L1 expression in their tumor cells, but one complete responder had PD-L2–positive malignant cells.
Dr. Ansell and his colleagues wrote that the “biologic basis for response in the other two [complete responders] is unclear,” and the researchers were unable to assess associations between response and c-myc expression or double-hit lymphoma.
Safety
Of all 121 patients, 62% had a treatment-related adverse event (AE) and 24% had a grade 3/4–related AE.
The most common related AEs of any grade were nausea (17%), fatigue (17%), diarrhea (10%), neutropenia (7%), thrombocytopenia (6%), decreased appetite (6%), lipase increase (5%), rash (5%), and pyrexia (5%).
Four patients (3%) stopped taking nivolumab because of treatment-related AEs, including neutropenia, thrombocytopenia, diarrhea, pancreatitis, lipase increase, and psoriasiform dermatitis. There were no fatal treatment-related AEs.
This research was supported by Bristol-Myers Squibb and other groups. The study authors reported relationships with Bristol-Myers Squibb and other companies.
SOURCE: Ansell SM et al. J Clin Oncol. 2019 Jan 8. doi: 10.1200/JCO.18.00766.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point:
Major finding: Nivolumab produced a response in 10 of 121 patients, including three complete responses.
Study details: A phase 2 study of 121 patients with relapsed/refractory diffuse large B-cell lymphoma.
Disclosures: This research was supported by Bristol-Myers Squibb and other organizations. The study authors reported relationships with Bristol-Myers Squibb and other companies.
Source: Ansell SM et al. J Clin Oncol. 2019 Jan 8. doi: 10.1200/JCO.18.00766.