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

Armand P.; Rodig S.; Melnichenko V.; Thieblemont C.; Bouabdallah K.; Tumyan G.; Özcan M.; Portino S.; Fogliatto L.; Caballero M.D.; Walewski J.; Gulbas Z.; Ribrag V.; Christian B.; Perini G.F.; et. al.


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. (C) 2019 by American Society of Clinical Oncology

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Título según WOS: Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma
Título según SCOPUS: Pembrolizumab in relapsed or refractory primary mediastinal large b-cell lymphoma
Volumen: 37
Número: 34
Fecha de publicación: 2019
Página de inicio: 3291
Página final: +
Idioma: English