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Nivolumab for relapsed/refractory diffuse large B-Cell lymphoma in patients ineligible for or having failed autologous transplantation: a single-arm, Phase II Study

Nivolumab for relapsed/refractory diffuse large B-Cell lymphoma in patients ineligible for or having failed autologous transplantation: a single-arm, Phase II Study
Nivolumab for relapsed/refractory diffuse large B-Cell lymphoma in patients ineligible for or having failed autologous transplantation: a single-arm, Phase II Study

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.

1527-7755
481-489
Ansell, Stephen M.
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Minnema, Monique C.
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Johnson, Peter
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Timmerman, John M.
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Armand, Philippe
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Shipp, Margaret A.
5266b107-0e50-4de5-a808-56f7cb92a78d
Rodig, Scott J.
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Ligon, Azra H.
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Roemer, Margaretha G.M.
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Reddy, Nishitha
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Cohen, Jonathon B.
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Assouline, Sarit
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Poon, Michelle
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Sharma, Manish
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Kato, Kazunobu
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Samakoglu, Selda
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Sumbul, Anne
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Grigg, Andrew
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Ansell, Stephen M.
8bc317a8-9c66-4734-af58-5de0562131a9
Minnema, Monique C.
77d4ff25-dede-4952-9d57-14f3045ec25b
Johnson, Peter
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Timmerman, John M.
06142895-1851-4d75-aaae-1eab05afe127
Armand, Philippe
6c7c559a-0d31-4c9d-9630-a2313dcd7c06
Shipp, Margaret A.
5266b107-0e50-4de5-a808-56f7cb92a78d
Rodig, Scott J.
02828be6-6ac7-48b4-af08-0ac8e43800a5
Ligon, Azra H.
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Roemer, Margaretha G.M.
af2c0b3d-cce8-4083-90bf-1e5d126f0e40
Reddy, Nishitha
609ca886-b51d-46de-b71a-9c12d821ab33
Cohen, Jonathon B.
245e35f9-aadf-4976-9927-7f3ccaf0632e
Assouline, Sarit
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Poon, Michelle
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Sharma, Manish
e8259260-c388-4d60-86c8-e95c35ae9a59
Kato, Kazunobu
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Samakoglu, Selda
2435cd95-707e-4702-b54f-30ca43001782
Sumbul, Anne
b87896c1-8aff-4a10-a8bd-e573f62d14bf
Grigg, Andrew
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Ansell, Stephen M., 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 and Grigg, Andrew (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, 37 (6), 481-489. (doi:10.1200/JCO.18.00766).

Record type: Article

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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S1_Nivo 139 DLBCL - Accepted Manuscript
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Accepted/In Press date: 13 November 2018
e-pub ahead of print date: 8 January 2019
Published date: 20 February 2019

Identifiers

Local EPrints ID: 428928
URI: https://eprints.soton.ac.uk/id/eprint/428928
ISSN: 1527-7755
PURE UUID: bb447b77-b78a-434f-ba9d-151bac7b6868
ORCID for Peter Johnson: ORCID iD orcid.org/0000-0003-2306-4974

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Date deposited: 14 Mar 2019 17:30
Last modified: 15 Mar 2019 01:36

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Contributors

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

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