Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A Single-Arm, Phase II Study

Stephen Maxted Ansell, Monique C. Minnema, Peter Johnson, John M. Timmerman, Philippe Armand, Margaret A. Shipp, Scott J. Rodig, Azra H. Ligon, Margaretha G.M. Roemer, Nishitha Reddy, Jonathon B. Cohen, Sarit Assouline, Michelle Poon, Manish Sharma, Kazunobu Kato, Selda Samakoglu, Anne Sumbul, Andrew Grigg

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)481-489
Number of pages9
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume37
Issue number6
DOIs
StatePublished - Feb 20 2019

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Lymphoma, Large B-Cell, Diffuse
Autologous Transplantation
Cell Transplantation
Safety
nivolumab
Neutropenia
Lipase
Disease-Free Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation : A Single-Arm, Phase II Study. / Ansell, Stephen Maxted; Minnema, Monique C.; Johnson, Peter; Timmerman, John M.; Armand, Philippe; Shipp, Margaret A.; Rodig, Scott J.; Ligon, Azra H.; Roemer, Margaretha G.M.; Reddy, Nishitha; Cohen, Jonathon B.; Assouline, Sarit; Poon, Michelle; Sharma, Manish; Kato, Kazunobu; Samakoglu, Selda; Sumbul, Anne; Grigg, Andrew.

In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Vol. 37, No. 6, 20.02.2019, p. 481-489.

Research output: Contribution to journalArticle

Ansell, SM, Minnema, MC, Johnson, P, Timmerman, JM, Armand, P, Shipp, MA, Rodig, SJ, Ligon, AH, Roemer, MGM, Reddy, N, Cohen, JB, Assouline, S, Poon, M, Sharma, M, Kato, K, Samakoglu, S, Sumbul, A & Grigg, A 2019, 'Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A Single-Arm, Phase II Study', Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol. 37, no. 6, pp. 481-489. https://doi.org/10.1200/JCO.18.00766
Ansell, Stephen Maxted ; Minnema, Monique C. ; Johnson, Peter ; Timmerman, John M. ; Armand, Philippe ; Shipp, Margaret A. ; Rodig, Scott J. ; Ligon, Azra H. ; Roemer, Margaretha G.M. ; Reddy, Nishitha ; Cohen, Jonathon B. ; Assouline, Sarit ; Poon, Michelle ; Sharma, Manish ; Kato, Kazunobu ; Samakoglu, Selda ; Sumbul, Anne ; Grigg, Andrew. / Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation : A Single-Arm, Phase II Study. In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019 ; Vol. 37, No. 6. pp. 481-489.
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abstract = "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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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 Maxted

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

PY - 2019/2/20

Y1 - 2019/2/20

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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