Dataset Information

Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma.

ABSTRACT: PURPOSE:Patients with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL) have a poor prognosis, and their treatment represents an urgent and unmet need. Because PMBCL is associated with genetic aberrations at 9p24 and overexpression of programmed cell death-1 (PD-1) ligands (PD-L1), it is hypothesized to be susceptible to PD-1 blockade. METHODS:In the phase IB KEYNOTE-013 (ClinicalTrials.gov identifier: NCT01953692) and phase II KEYNOTE-170 (ClinicalTrials.gov identifier: NCT02576990) studies, adults with rrPMBCL received pembrolizumab for up to 2 years or until disease progression or unacceptable toxicity. The primary end points were safety and objective response rate in KEYNOTE-013 and objective response rate in KEYNOTE-170. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Exploratory end points included association between biomarkers and pembrolizumab activity. RESULTS:The objective response rate was 48% (7 complete responses; 33%) among 21 patients in KEYNOTE-013 and 45% (7 complete responses; 13%) among 53 patients in KEYNOTE-170. After a median follow-up time of 29.1 months in KEYNOTE-013 and 12.5 months in KEYNOTE-170, the median duration of response was not reached in either study. No patient with complete response experienced progression, including 2 patients with complete response for at least 1 year off therapy. Treatment-related adverse events occurred in 24% of patients in KEYNOTE-013 and 23% of patients in KEYNOTE-170. There were no treatment-related deaths. Among 42 evaluable patients, the magnitude of the 9p24 gene abnormality was associated with PD-L1 expression, which was itself significantly associated with progression-free survival. CONCLUSION:Pembrolizumab is associated with high response rate, durable activity, and a manageable safety profile in patients with rrPMBCL.

SUBMITTER: Armand P

PROVIDER: S-EPMC6881098 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma.

Armand Philippe P Rodig Scott S Melnichenko Vladimir V Thieblemont Catherine C Bouabdallah Kamal K Tumyan Gayane G Özcan Muhit M Portino Sergio S Fogliatto Laura L Caballero Maria D MD Walewski Jan J Gulbas Zafer Z Ribrag Vincent V Christian Beth B Perini Guilherme Fleury GF Salles Gilles G Svoboda Jakub J Zain Jasmine J Patel Sanjay S Chen Pei-Hsuan PH Ligon Azra H AH Ouyang Jing J Neuberg Donna D Redd Robert R Chatterjee Arkendu A Balakumaran Arun A Orlowski Robert R Shipp Margaret M Zinzani Pier Luigi PL

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20191014 34

<h4>Purpose</h4>Patients with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL) have a poor prognosis, and their treatment represents an urgent and unmet need. Because PMBCL is associated with genetic aberrations at 9p24 and overexpression of programmed cell death-1 (PD-1) ligands (PD-L1), it is hypothesized to be susceptible to PD-1 blockade.<h4>Methods</h4>In the phase IB KEYNOTE-013 (ClinicalTrials.gov identifier: NCT01953692) and phase II KEYNOTE-170 (ClinicalTrials. ...[more]

PMID: 31609651

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Project description:PURPOSE:Primary mediastinal B-cell lymphoma (PMBL) is a rare but aggressive non-Hodgkin lymphoma with poor outcomes in patients with relapsed/refractory (R/R) disease. PMBL is characterized by high expression of programmed death-1 ligand and variable expression of CD30. Nivolumab, an anti-programmed death-1 immune checkpoint inhibitor, and brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, may have synergistic activity in R/R PMBL. METHODS:The expansion cohort of the open-label, phase I/II CheckMate 436 study enrolled patients with confirmed R/R PMBL who were previously treated with either autologous hematopoietic cell transplantation or two or more prior chemotherapy regimens if ineligible for autologous hematopoietic cell transplantation. Patients received nivolumab (240 mg intravenously) and BV (1.8 mg/kg intravenously) every 3 weeks until disease progression or unacceptable toxicity. Primary end points were investigator-assessed objective response rate (ORR) per the Lugano 2014 criteria and safety. RESULTS:Thirty patients with PMBL were treated and evaluable. At a median follow-up of 11.1 months, ORR (95% CI) was 73% (54% to 88%), with a 37% complete remission rate per investigator, and ORR of 70% (51% to 85%), with a 43% complete metabolic response rate per independent review. Median duration of response, median progression-free survival, and median overall survival have not been reached. Eleven responders had consolidation with autologous (n = 5) or allogeneic (n = 6) transplantation. Treatment-related adverse events were reported in 25 patients (83%). Sixteen patients (53%) had grade 3 to 4 treatment-related adverse events; the most common were neutropenia (n = 9), thrombocytopenia (n = 3), and peripheral neuropathy (n = 3). There were no treatment-related deaths. CONCLUSION:In patients with R/R PMBL, the combination of nivolumab plus BV represents a promising option, with high antitumor activity and a manageable safety profile.

Dataset Information

Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma.

Publications

Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma.

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