Nivolumab in patients with relapsed or refractory hematologic malignancy

Preliminary results of a phase ib study

Alexander M. Lesokhin, Stephen M. Ansell, Philippe Armand, Emma Scott, Ahmad Halwani, Martin Gutierrez, Michael M. Millenson, Adam D. Cohen, Stephen J. Schuster, Daniel Lebovic, Madhav Dhodapkar, David Avigan, Bjoern Chapuy, Azra H. Ligon, Gordon J. Freeman, Scott J. Rodig, Deepika Cattry, Lili Zhu, Joseph F. Grosso, M. Brigid Bradley Garelik & 3 others Margaret A. Shipp, Ivan Borrello, John Timmerman

Research output: Contribution to journalArticle

342 Citations (Scopus)

Abstract

Purpose Cancer cells can exploit the programmed death-1 (PD-1) immune checkpoint pathway to avoid immune surveillance by modulating T-lymphocyte activity. In part, this may occur through overexpression of PD-1 and PD-1 pathway ligands (PD-L1 and PD-L2) in the tumor microenvironment. PD-1 blockade has produced significant antitumor activity in solid tumors, and similar evidence has emerged in hematologic malignancies. Methods In this phase I, open-label, dose-escalation, cohort-expansion study, patients with relapsed or refractory B-cell lymphoma, T-cell lymphoma, and multiple myeloma received the anti-PD-1 monoclonal antibody nivolumab at doses of 1 or 3 mg/kg every 2 weeks. This study aimed to evaluate the safety and efficacy of nivolumab and to assess PD-L1/PD-L2 locus integrity and protein expression. Results Eighty-one patients were treated (follicular lymphoma, n = 10; diffuse large B-cell lymphoma, n = 11; other B-cell lymphomas, n = 10; mycosis fungoides, n = 13; peripheral T-cell lymphoma, n = 5; other T-cell lymphomas, n = 5; multiple myeloma, n = 27). Patients had received a median of three (range, one to 12) prior systemic treatments. Drug-related adverse events occurred in 51 (63%) patients, and most were grade 1 or 2. Objective response rates were 40%, 36%, 15%, and 40% among patients with follicular lymphoma, diffuse large B-cell lymphoma, mycosis fungoides, and peripheral T-cell lymphoma, respectively. Median time of follow-up observation was 66.6 weeks (range, 1.6 to 132.0+ weeks). Durations of response in individual patients ranged from 6.0 to 81.6+ weeks. Conclusion Nivolumab was well tolerated and exhibited antitumor activity in extensively pretreated patients with relapsed or refractory B-and T-cell lymphomas. Additional studies of nivolumab in these diseases are ongoing.

Original languageEnglish (US)
Pages (from-to)2698-2704
Number of pages7
JournalJournal of Clinical Oncology
Volume34
Issue number23
DOIs
StatePublished - Aug 10 2016

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Hematologic Neoplasms
T-Cell Lymphoma
B-Cell Lymphoma
Peripheral T-Cell Lymphoma
Mycosis Fungoides
Follicular Lymphoma
Lymphoma, Large B-Cell, Diffuse
Multiple Myeloma
Tumor Microenvironment
nivolumab
Drug-Related Side Effects and Adverse Reactions
Neoplasms
Cohort Studies
Monoclonal Antibodies
Observation
Ligands
T-Lymphocytes
Safety
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Nivolumab in patients with relapsed or refractory hematologic malignancy : Preliminary results of a phase ib study. / Lesokhin, Alexander M.; Ansell, Stephen M.; Armand, Philippe; Scott, Emma; Halwani, Ahmad; Gutierrez, Martin; Millenson, Michael M.; Cohen, Adam D.; Schuster, Stephen J.; Lebovic, Daniel; Dhodapkar, Madhav; Avigan, David; Chapuy, Bjoern; Ligon, Azra H.; Freeman, Gordon J.; Rodig, Scott J.; Cattry, Deepika; Zhu, Lili; Grosso, Joseph F.; Brigid Bradley Garelik, M.; Shipp, Margaret A.; Borrello, Ivan; Timmerman, John.

In: Journal of Clinical Oncology, Vol. 34, No. 23, 10.08.2016, p. 2698-2704.

Research output: Contribution to journalArticle

Lesokhin, AM, Ansell, SM, Armand, P, Scott, E, Halwani, A, Gutierrez, M, Millenson, MM, Cohen, AD, Schuster, SJ, Lebovic, D, Dhodapkar, M, Avigan, D, Chapuy, B, Ligon, AH, Freeman, GJ, Rodig, SJ, Cattry, D, Zhu, L, Grosso, JF, Brigid Bradley Garelik, M, Shipp, MA, Borrello, I & Timmerman, J 2016, 'Nivolumab in patients with relapsed or refractory hematologic malignancy: Preliminary results of a phase ib study', Journal of Clinical Oncology, vol. 34, no. 23, pp. 2698-2704. https://doi.org/10.1200/JCO.2015.65.9789
Lesokhin, Alexander M. ; Ansell, Stephen M. ; Armand, Philippe ; Scott, Emma ; Halwani, Ahmad ; Gutierrez, Martin ; Millenson, Michael M. ; Cohen, Adam D. ; Schuster, Stephen J. ; Lebovic, Daniel ; Dhodapkar, Madhav ; Avigan, David ; Chapuy, Bjoern ; Ligon, Azra H. ; Freeman, Gordon J. ; Rodig, Scott J. ; Cattry, Deepika ; Zhu, Lili ; Grosso, Joseph F. ; Brigid Bradley Garelik, M. ; Shipp, Margaret A. ; Borrello, Ivan ; Timmerman, John. / Nivolumab in patients with relapsed or refractory hematologic malignancy : Preliminary results of a phase ib study. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 23. pp. 2698-2704.
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abstract = "Purpose Cancer cells can exploit the programmed death-1 (PD-1) immune checkpoint pathway to avoid immune surveillance by modulating T-lymphocyte activity. In part, this may occur through overexpression of PD-1 and PD-1 pathway ligands (PD-L1 and PD-L2) in the tumor microenvironment. PD-1 blockade has produced significant antitumor activity in solid tumors, and similar evidence has emerged in hematologic malignancies. Methods In this phase I, open-label, dose-escalation, cohort-expansion study, patients with relapsed or refractory B-cell lymphoma, T-cell lymphoma, and multiple myeloma received the anti-PD-1 monoclonal antibody nivolumab at doses of 1 or 3 mg/kg every 2 weeks. This study aimed to evaluate the safety and efficacy of nivolumab and to assess PD-L1/PD-L2 locus integrity and protein expression. Results Eighty-one patients were treated (follicular lymphoma, n = 10; diffuse large B-cell lymphoma, n = 11; other B-cell lymphomas, n = 10; mycosis fungoides, n = 13; peripheral T-cell lymphoma, n = 5; other T-cell lymphomas, n = 5; multiple myeloma, n = 27). Patients had received a median of three (range, one to 12) prior systemic treatments. Drug-related adverse events occurred in 51 (63{\%}) patients, and most were grade 1 or 2. Objective response rates were 40{\%}, 36{\%}, 15{\%}, and 40{\%} among patients with follicular lymphoma, diffuse large B-cell lymphoma, mycosis fungoides, and peripheral T-cell lymphoma, respectively. Median time of follow-up observation was 66.6 weeks (range, 1.6 to 132.0+ weeks). Durations of response in individual patients ranged from 6.0 to 81.6+ weeks. Conclusion Nivolumab was well tolerated and exhibited antitumor activity in extensively pretreated patients with relapsed or refractory B-and T-cell lymphomas. Additional studies of nivolumab in these diseases are ongoing.",
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T1 - Nivolumab in patients with relapsed or refractory hematologic malignancy

T2 - Preliminary results of a phase ib study

AU - Lesokhin, Alexander M.

AU - Ansell, Stephen M.

AU - Armand, Philippe

AU - Scott, Emma

AU - Halwani, Ahmad

AU - Gutierrez, Martin

AU - Millenson, Michael M.

AU - Cohen, Adam D.

AU - Schuster, Stephen J.

AU - Lebovic, Daniel

AU - Dhodapkar, Madhav

AU - Avigan, David

AU - Chapuy, Bjoern

AU - Ligon, Azra H.

AU - Freeman, Gordon J.

AU - Rodig, Scott J.

AU - Cattry, Deepika

AU - Zhu, Lili

AU - Grosso, Joseph F.

AU - Brigid Bradley Garelik, M.

AU - Shipp, Margaret A.

AU - Borrello, Ivan

AU - Timmerman, John

PY - 2016/8/10

Y1 - 2016/8/10

N2 - Purpose Cancer cells can exploit the programmed death-1 (PD-1) immune checkpoint pathway to avoid immune surveillance by modulating T-lymphocyte activity. In part, this may occur through overexpression of PD-1 and PD-1 pathway ligands (PD-L1 and PD-L2) in the tumor microenvironment. PD-1 blockade has produced significant antitumor activity in solid tumors, and similar evidence has emerged in hematologic malignancies. Methods In this phase I, open-label, dose-escalation, cohort-expansion study, patients with relapsed or refractory B-cell lymphoma, T-cell lymphoma, and multiple myeloma received the anti-PD-1 monoclonal antibody nivolumab at doses of 1 or 3 mg/kg every 2 weeks. This study aimed to evaluate the safety and efficacy of nivolumab and to assess PD-L1/PD-L2 locus integrity and protein expression. Results Eighty-one patients were treated (follicular lymphoma, n = 10; diffuse large B-cell lymphoma, n = 11; other B-cell lymphomas, n = 10; mycosis fungoides, n = 13; peripheral T-cell lymphoma, n = 5; other T-cell lymphomas, n = 5; multiple myeloma, n = 27). Patients had received a median of three (range, one to 12) prior systemic treatments. Drug-related adverse events occurred in 51 (63%) patients, and most were grade 1 or 2. Objective response rates were 40%, 36%, 15%, and 40% among patients with follicular lymphoma, diffuse large B-cell lymphoma, mycosis fungoides, and peripheral T-cell lymphoma, respectively. Median time of follow-up observation was 66.6 weeks (range, 1.6 to 132.0+ weeks). Durations of response in individual patients ranged from 6.0 to 81.6+ weeks. Conclusion Nivolumab was well tolerated and exhibited antitumor activity in extensively pretreated patients with relapsed or refractory B-and T-cell lymphomas. Additional studies of nivolumab in these diseases are ongoing.

AB - Purpose Cancer cells can exploit the programmed death-1 (PD-1) immune checkpoint pathway to avoid immune surveillance by modulating T-lymphocyte activity. In part, this may occur through overexpression of PD-1 and PD-1 pathway ligands (PD-L1 and PD-L2) in the tumor microenvironment. PD-1 blockade has produced significant antitumor activity in solid tumors, and similar evidence has emerged in hematologic malignancies. Methods In this phase I, open-label, dose-escalation, cohort-expansion study, patients with relapsed or refractory B-cell lymphoma, T-cell lymphoma, and multiple myeloma received the anti-PD-1 monoclonal antibody nivolumab at doses of 1 or 3 mg/kg every 2 weeks. This study aimed to evaluate the safety and efficacy of nivolumab and to assess PD-L1/PD-L2 locus integrity and protein expression. Results Eighty-one patients were treated (follicular lymphoma, n = 10; diffuse large B-cell lymphoma, n = 11; other B-cell lymphomas, n = 10; mycosis fungoides, n = 13; peripheral T-cell lymphoma, n = 5; other T-cell lymphomas, n = 5; multiple myeloma, n = 27). Patients had received a median of three (range, one to 12) prior systemic treatments. Drug-related adverse events occurred in 51 (63%) patients, and most were grade 1 or 2. Objective response rates were 40%, 36%, 15%, and 40% among patients with follicular lymphoma, diffuse large B-cell lymphoma, mycosis fungoides, and peripheral T-cell lymphoma, respectively. Median time of follow-up observation was 66.6 weeks (range, 1.6 to 132.0+ weeks). Durations of response in individual patients ranged from 6.0 to 81.6+ weeks. Conclusion Nivolumab was well tolerated and exhibited antitumor activity in extensively pretreated patients with relapsed or refractory B-and T-cell lymphomas. Additional studies of nivolumab in these diseases are ongoing.

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