Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin Lymphoma

Robert Chen, Pier Luigi Zinzani, Michelle A. Fanale, Philippe Armand, Nathalie A. Johnson, Pauline Brice, John Radford, Vincent Ribrag, Daniel Molin, Theodoros P. Vassilakopoulos, Akihiro Tomita, Bastian Von Tresckow, Margaret A. Shipp, Yinghua Zhang, Alejandro D. Ricart, Arun Balakumaran, Craig H. Moskowitz

Research output: Contribution to journalArticle

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Abstract

Purpose: Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods: KEYNOTE-087 (ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results: A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response $6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion: Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease.

Original languageEnglish
Pages (from-to)2125-2132
Number of pages8
JournalJournal of Clinical Oncology
Volume35
Issue number19
DOIs
Publication statusPublished - 01-07-2017

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Hodgkin Disease
Safety
Stem Cell Transplantation
Programmed Cell Death 1 Ligand 2 Protein
Reed-Sternberg Cells
Blocking Antibodies
pembrolizumab
Lymphoma
Chromosomes
Transplantation
Drug Therapy
Therapeutics
cAC10-vcMMAE

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Chen, R., Zinzani, P. L., Fanale, M. A., Armand, P., Johnson, N. A., Brice, P., ... Moskowitz, C. H. (2017). Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin Lymphoma. Journal of Clinical Oncology, 35(19), 2125-2132. https://doi.org/10.1200/JCO.2016.72.1316
Chen, Robert ; Zinzani, Pier Luigi ; Fanale, Michelle A. ; Armand, Philippe ; Johnson, Nathalie A. ; Brice, Pauline ; Radford, John ; Ribrag, Vincent ; Molin, Daniel ; Vassilakopoulos, Theodoros P. ; Tomita, Akihiro ; Von Tresckow, Bastian ; Shipp, Margaret A. ; Zhang, Yinghua ; Ricart, Alejandro D. ; Balakumaran, Arun ; Moskowitz, Craig H. / Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin Lymphoma. In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 19. pp. 2125-2132.
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abstract = "Purpose: Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods: KEYNOTE-087 (ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results: A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0{\%} (95{\%} CI, 62.3{\%} to 75.2{\%}), and the complete response rate was 22.4{\%} (95{\%} CI, 16.9{\%} to 28.6{\%}). By cohort, ORRs were 73.9{\%} for cohort 1, 64.2{\%} for cohort 2, and 70.0{\%} for cohort 3. Thirty-one patients had a response $6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion: Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease.",
author = "Robert Chen and Zinzani, {Pier Luigi} and Fanale, {Michelle A.} and Philippe Armand and Johnson, {Nathalie A.} and Pauline Brice and John Radford and Vincent Ribrag and Daniel Molin and Vassilakopoulos, {Theodoros P.} and Akihiro Tomita and {Von Tresckow}, Bastian and Shipp, {Margaret A.} and Yinghua Zhang and Ricart, {Alejandro D.} and Arun Balakumaran and Moskowitz, {Craig H.}",
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Chen, R, Zinzani, PL, Fanale, MA, Armand, P, Johnson, NA, Brice, P, Radford, J, Ribrag, V, Molin, D, Vassilakopoulos, TP, Tomita, A, Von Tresckow, B, Shipp, MA, Zhang, Y, Ricart, AD, Balakumaran, A & Moskowitz, CH 2017, 'Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin Lymphoma', Journal of Clinical Oncology, vol. 35, no. 19, pp. 2125-2132. https://doi.org/10.1200/JCO.2016.72.1316

Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin Lymphoma. / Chen, Robert; Zinzani, Pier Luigi; Fanale, Michelle A.; Armand, Philippe; Johnson, Nathalie A.; Brice, Pauline; Radford, John; Ribrag, Vincent; Molin, Daniel; Vassilakopoulos, Theodoros P.; Tomita, Akihiro; Von Tresckow, Bastian; Shipp, Margaret A.; Zhang, Yinghua; Ricart, Alejandro D.; Balakumaran, Arun; Moskowitz, Craig H.

In: Journal of Clinical Oncology, Vol. 35, No. 19, 01.07.2017, p. 2125-2132.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin Lymphoma

AU - Chen, Robert

AU - Zinzani, Pier Luigi

AU - Fanale, Michelle A.

AU - Armand, Philippe

AU - Johnson, Nathalie A.

AU - Brice, Pauline

AU - Radford, John

AU - Ribrag, Vincent

AU - Molin, Daniel

AU - Vassilakopoulos, Theodoros P.

AU - Tomita, Akihiro

AU - Von Tresckow, Bastian

AU - Shipp, Margaret A.

AU - Zhang, Yinghua

AU - Ricart, Alejandro D.

AU - Balakumaran, Arun

AU - Moskowitz, Craig H.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Purpose: Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods: KEYNOTE-087 (ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results: A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response $6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion: Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease.

AB - Purpose: Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods: KEYNOTE-087 (ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results: A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response $6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion: Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease.

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