TY - JOUR
T1 - Nivolumab for relapsed/refractory diffuse large B-cell lymphoma in patients ineligible for or having failed autologous transplantation
T2 - A single-arm, phase II study
AU - Ansell, Stephen M.
AU - Minnema, Monique C.
AU - Johnson, Peter
AU - Timmerman, John M.
AU - Armand, Philippe
AU - Shipp, Margaret A.
AU - Rodig, Scott J.
AU - Ligon, Azra H.
AU - Roemer, Margaretha G.M.
AU - Reddy, Nishitha
AU - Cohen, Jonathon B.
AU - Assouline, Sarit
AU - Poon, Michelle
AU - Sharma, Manish
AU - Kato, Kazunobu
AU - Samakoglu, Selda
AU - Sumbul, Anne
AU - Grigg, Andrew
N1 - Funding Information:
Supported by Bristol-Myers Squibb, which also funded medical writing support. Also supported by the Harold and Virginia Lash Foundation (P.A.); US National Institutes of Health Grant No. R01CA161026 and the Miller Fund (M.A.S.); the Center for Immuno-Oncology of the Dana-Farber Cancer Institute (S.J.R.); and the American Society of Hematology and Lymphoma Research Foundation (388017; J.B.C.).
Publisher Copyright:
© 2019 by American Society of Clinical Oncology.
PY - 2019
Y1 - 2019
N2 - PURPOSE Treatment options are limited for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Tumor cells can exploit the programmed death-1 checkpoint pathway to evade immune surveillance. In the current study, we evaluated the efficacy and safety of programmed death-1 blockade by nivolumab in patients with relapsed/refractory DLBCL. METHODS In this phase II, open-label study, patients with relapsed/refractory DLBCL who were ineligible for autologous hematopoietic cell transplantation (auto-HCT) or who had experienced failure with auto-HCT received nivolumab 3 mg/kg every 2 weeks. We assessed the efficacy and safety of nivolumab as well as genetic alterations of 9p24.1. RESULTS Among 121 treated patients, patients in the auto-HCT–failed cohort (n = 87) received a median of four nivolumab doses and a median of three doses were administered to those in the auto-HCT–ineligible cohort (n = 34). At a median follow-up of 9 months in the auto-HCT–failed cohort and 6 months in the auto-HCT–ineligible cohort, independently assessed objective response rates were 10% and 3%, and median durations of response were 11 and 8 months, respectively. Median progression-free survival and overall survival were 1.9 and 12.2 months in the auto-HCT–failed cohort and 1.4 and 5.8 months in the auto-HCT–ineligible cohort respectively. All three patients with complete remission—3% of the auto-HCT–failed cohort—had durable response (11 or more, 14 or more, and 17 months). Treatment-related grade 3 and 4 adverse events were reported in 24% of patients. The most common were neutropenia (4%), thrombocytopenia (3%), and increased lipase (3%). Of all evaluable samples for 9p24.1 analysis, 16% exhibited low-level copy gain and 3% had amplification. CONCLUSION Nivolumab monotherapy is associated with a favorable safety profile but a low overall response rate among patients with DLBCL who are ineligible for auto-HCT or who experienced failure with auto-HCT. Genetic alterations of 9p24.1 are infrequent in DLBCL.
AB - PURPOSE Treatment options are limited for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Tumor cells can exploit the programmed death-1 checkpoint pathway to evade immune surveillance. In the current study, we evaluated the efficacy and safety of programmed death-1 blockade by nivolumab in patients with relapsed/refractory DLBCL. METHODS In this phase II, open-label study, patients with relapsed/refractory DLBCL who were ineligible for autologous hematopoietic cell transplantation (auto-HCT) or who had experienced failure with auto-HCT received nivolumab 3 mg/kg every 2 weeks. We assessed the efficacy and safety of nivolumab as well as genetic alterations of 9p24.1. RESULTS Among 121 treated patients, patients in the auto-HCT–failed cohort (n = 87) received a median of four nivolumab doses and a median of three doses were administered to those in the auto-HCT–ineligible cohort (n = 34). At a median follow-up of 9 months in the auto-HCT–failed cohort and 6 months in the auto-HCT–ineligible cohort, independently assessed objective response rates were 10% and 3%, and median durations of response were 11 and 8 months, respectively. Median progression-free survival and overall survival were 1.9 and 12.2 months in the auto-HCT–failed cohort and 1.4 and 5.8 months in the auto-HCT–ineligible cohort respectively. All three patients with complete remission—3% of the auto-HCT–failed cohort—had durable response (11 or more, 14 or more, and 17 months). Treatment-related grade 3 and 4 adverse events were reported in 24% of patients. The most common were neutropenia (4%), thrombocytopenia (3%), and increased lipase (3%). Of all evaluable samples for 9p24.1 analysis, 16% exhibited low-level copy gain and 3% had amplification. CONCLUSION Nivolumab monotherapy is associated with a favorable safety profile but a low overall response rate among patients with DLBCL who are ineligible for auto-HCT or who experienced failure with auto-HCT. Genetic alterations of 9p24.1 are infrequent in DLBCL.
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U2 - 10.1200/JCO.18.00766
DO - 10.1200/JCO.18.00766
M3 - Article
C2 - 30620669
AN - SCOPUS:85061589693
SN - 0732-183X
VL - 37
SP - 481
EP - 489
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 6
ER -