1. Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma
- Author
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Arun Balakumaran, Jean-Marie Michot, Yayan Zhang, Pier Luigi Zinzani, S. Chlosta, Margaret A. Shipp, Craig H. Moskowitz, Philippe Armand, Vincent Ribrag, John Kuruvilla, Zinzani, Pier Luigi, Ribrag, Vincent, Moskowitz, Craig H, Michot, Jean-Marie, Kuruvilla, John, Balakumaran, Arun, Zhang, Yayan, Chlosta, Sabine, Shipp, Margaret A, and Armand, Philippe
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,large B-cell lymphoma, KEYNOTE-013 ,Lymphoma ,Clinical Trials and Observations ,Immunology ,Programmed Cell Death 1 Receptor ,Gene Expression ,Antineoplastic Agents ,Pembrolizumab ,Antibodies, Monoclonal, Humanized ,Biochemistry ,Gastroenterology ,Mediastinal Neoplasms ,Drug Administration Schedule ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,Internal medicine ,medicine ,Humans ,Adverse effect ,Survival analysis ,business.industry ,Cell Biology ,Hematology ,medicine.disease ,Prognosis ,Survival Analysis ,Surgery ,Blockade ,Clinical trial ,030104 developmental biology ,Treatment Outcome ,Tolerability ,030220 oncology & carcinogenesis ,Female ,Lymphoma, Large B-Cell, Diffuse ,Patient Safety ,Neoplasm Recurrence, Local ,business - Abstract
Treatment options for relapsed/refractory primary mediastinal large B-cell lymphoma (rrPMBCL) are limited, and prognosis is generally poor (overall response rate [ORR] 0% to 25%; 2-year overall survival 15%). PMBCL frequently involves PD-1 ligand overexpression, potentially making PMBCL particularly susceptible to PD-1 blockade. We evaluated safety and antitumor activity of pembrolizumab, an anti-PD-1 antibody, in rrPMBCL as part of the KEYNOTE-013 multicohort phase 1b trial. At time of data cutoff, 18 patients (median age 30 years; median 3 prior lines of therapy) had been enrolled and treated, of whom 17 were included in the efficacy analyses. Eleven patients (61%) experienced drug-related adverse events (mostly grade 1-2); none discontinued treatment due to adverse events. ORR was 41% (7/17); 6 additional patients (35%) had stable disease. Of patients evaluable by imaging, 13 out of 16 (81%) had decreases in target lesions. With a median follow-up of 11.3 months, median duration of response was not reached. Two patients reached the maximum 2-year treatment duration and remain in remission. Median overall survival was not reached for treated patients overall; all responders were still alive at data cutoff. These results in heavily pretreated rrPMBCL patients demonstrate that PD-1 blockade with pembrolizumab has a manageable safety profile and promising antitumor activity. This trial was registered at www.clinicaltrials.gov as #NCT01953692.
- Published
- 2016