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

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
Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 2019 December 1, 37 (34): 3291-3299

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 ( identifier: NCT01953692) and phase II KEYNOTE-170 ( 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.

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