Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure

Philippe Armand; Margaret A Shipp; Vincent Ribrag; Jean-Marie Michot; Pier Luigi Zinzani; John Kuruvilla; Ellen S Snyder; Alejandro D Ricart; Arun Balakumaran; Shelonitda Rose; Craig H Moskowitz

doi:10.1200/JCO.2016.67.3467

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Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure

Journal article

Open access

Peer reviewed

Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure

Philippe Armand, Margaret A Shipp, Vincent Ribrag, Jean-Marie Michot, Pier Luigi Zinzani, John Kuruvilla, Ellen S Snyder, Alejandro D Ricart, Arun Balakumaran, Shelonitda Rose, …

Journal of clinical oncology, Vol.34(31), pp.3733-3739

2016-11-01

DOI: https://doi.org/10.1200/JCO.2016.67.3467

PMCID: PMC5791838

PMID: 27354476

Abstract

Adult

Aged

Antibodies, Monoclonal, Humanized - adverse effects

Antibodies, Monoclonal, Humanized - therapeutic use

Antineoplastic Agents, Immunological - adverse effects

Antineoplastic Agents, Immunological - therapeutic use

B7-H1 Antigen - metabolism

Cohort Studies

Disease-Free Survival

Female

Hodgkin Disease - drug therapy

Hodgkin Disease - metabolism

Humans

Immunoconjugates - therapeutic use

Male

Middle Aged

Programmed Cell Death 1 Receptor - antagonists & inhibitors

Programmed Cell Death 1 Receptor - metabolism

Remission Induction

Treatment Failure

Young Adult

Purpose Classical Hodgkin lymphoma (HL) frequently exhibits genetic alterations leading to overexpression of the programmed death-1 (PD-1) ligands, suggesting a possible vulnerability to PD-1 blockade. The phase Ib study KEYNOTE-013 (NCT01953692) tested the safety and efficacy of the anti-PD-1 antibody pembrolizumab in patients with hematologic malignancies. Based on its genetics, HL was included as an independent cohort. Methods We enrolled patients with relapsed or refractory HL whose disease progressed on or after treatment with brentuximab vedotin. Patients received pembrolizumab, 10 mg/kg every 2 weeks, until disease progression occurred. Response to treatment was assessed at week 12 and every 8 weeks thereafter. Principal end points were safety and complete remission (CR) rate. Results Thirty-one patients were enrolled; 55% had more than four lines of prior therapy, and 71% had relapsed after autologous stem cell transplantation. Five patients (16%) experienced grade 3 drug-related adverse events (AEs); there were no grade 4 AEs or deaths related to treatment. The CR rate was 16% (90% CI, 7% to 31%). In addition, 48% of patients achieved a partial remission, for an overall response rate of 65% (90% CI, 48% to 79%). Most of the responses (70%) lasted longer than 24 weeks (range, 0.14+ to 74+ weeks), with a median follow-up of 17 months. The progression-free survival rate was 69% at 24 weeks and 46% at 52 weeks. Biomarker analyses demonstrated a high prevalence of PD-L1 and PD-L2 expression, treatment-induced expansion of T cells and natural killer cells, and activation of interferon-γ, T-cell receptor, and expanded immune-related signaling pathways. Conclusions Pembrolizumab was associated with a favorable safety profile. Pembrolizumab treatment induced favorable responses in a heavily pretreated patient cohort, justifying further studies.

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Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.6 Immunology; 1.6.214 PD-1
Web Of Science research areas: Oncology
ESI research areas: Clinical Medicine

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Title: Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure
Creators: Philippe Armand - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; Pier Luigi Zinzani, Institute of Hematology Seràgnoli, University of Bologna, Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, Memorial Sloan Kettering Cancer Center, New York, NY
Margaret A Shipp - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; Pier Luigi Zinzani, Institute of Hematology Seràgnoli, University of Bologna, Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, Memorial Sloan Kettering Cancer Center, New York, NY
Vincent Ribrag - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; Pier Luigi Zinzani, Institute of Hematology Seràgnoli, University of Bologna, Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, Memorial Sloan Kettering Cancer Center, New York, NY
Jean-Marie Michot - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; Pier Luigi Zinzani, Institute of Hematology Seràgnoli, University of Bologna, Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, Memorial Sloan Kettering Cancer Center, New York, NY
Pier Luigi Zinzani - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; Pier Luigi Zinzani, Institute of Hematology Seràgnoli, University of Bologna, Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, Memorial Sloan Kettering Cancer Center, New York, NY
John Kuruvilla - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; Pier Luigi Zinzani, Institute of Hematology Seràgnoli, University of Bologna, Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, Memorial Sloan Kettering Cancer Center, New York, NY
Ellen S Snyder - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; Pier Luigi Zinzani, Institute of Hematology Seràgnoli, University of Bologna, Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, Memorial Sloan Kettering Cancer Center, New York, NY
Alejandro D Ricart - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; Pier Luigi Zinzani, Institute of Hematology Seràgnoli, University of Bologna, Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, Memorial Sloan Kettering Cancer Center, New York, NY
Arun Balakumaran - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; Pier Luigi Zinzani, Institute of Hematology Seràgnoli, University of Bologna, Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, Memorial Sloan Kettering Cancer Center, New York, NY
Shelonitda Rose - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; Pier Luigi Zinzani, Institute of Hematology Seràgnoli, University of Bologna, Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, Memorial Sloan Kettering Cancer Center, New York, NY
Craig H Moskowitz - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; Pier Luigi Zinzani, Institute of Hematology Seràgnoli, University of Bologna, Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, Memorial Sloan Kettering Cancer Center, New York, NY
Publication Details: Journal of clinical oncology, Vol.34(31), pp.3733-3739
Grant note: R01 CA161026 / NCI NIH HHS P30 CA008748 / NCI NIH HHS
Academic Unit: Miller School of Medicine; UMMG Department of Medicine
Language: English
Resource Type: Journal article
PMID: 27354476
PMCID: PMC5791838
Record Identifier: 991031613724802976