Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma
Year: 2019
Type: article
Study design: Clinical Trial
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.
Source: Journal of Clinical Oncology
DOI: 10.1200/jco.19.01389
Authors: Philippe Armand, Scott Rodig, Vladimir Melnichenko, Catherine Thieblemont, Kamal Bouabdallah, Gayane Tumyan, Muhit Özcan, Sergio Portino, Laura Fogliatto, Maria D. Caballero, Jan Walewski, Zafer Gulbas, Vincent Ribrag, Beth Christian, Guilherme Fleury Perini, Gilles Salles, Jakub Svoboda, Jasmine Zain, Sanjay Patel, Pei-Hsuan Chen, Azra H. Ligon, Jing Ouyang, Donna Neuberg, Robert Redd, Arkendu Chatterjee, Arun Balakumaran, Robert Orlowski, Margaret Shipp, Pier Luigi Zinzani
Institutions: Dana-Farber Cancer Institute, National Medical and Surgical Center named after N.I. Pirogov, Assistance Publique – Hôpitaux de Paris, Hôpital Saint-Louis, Hôpital Cardiologique du Haut-Lévêque, Russian Cancer Research Center NN Blokhin, Ankara University, Clínica Alemana, Hospital de Clínicas de Porto Alegre, Complejo Hospitalario de Salamanca, The Maria Sklodowska-Curie National Research Institute of Oncology, Institut Gustave Roussy, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Hospital Israelita Albert Einstein, Lyon 1 Université, University of Pennsylvania, City Of Hope National Medical Center, City of Hope, Brigham and Women's Hospital, Merck & Co., Inc., Rahway, NJ, USA (United States), University of Bologna
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W2979952645