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Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma.

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.

SUBMITTER: Zinzani PL

PROVIDER: S-EPMC5766837 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundHistone deacetylase inhibitor romidepsin has demonstrated durable clinical responses and tolerability in patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma (PTCL, CTCL). Selection of novel drug therapies for patients with relapsed/refractory aggressive lymphoma requires not only considerations regarding efficacy but also careful evaluation of toxicities as well as overall clinical benefit. The purpose of this analysis was to examine common adverse events (AEs) reported in pivotal trials of romidepsin in relapsed/refractory PTCL or CTCL and to more clearly define the overall AE profile in these populations.MethodsPatients with relapsed/refractory PTCL or CTCL were treated with romidepsin at 14 mg/m(2) as a 4-hour intravenous infusion on days 1, 8, and 15 of 28-day cycles for up to 6 cycles; patients with at least stable disease could extend therapy until progressive disease or another withdrawal criterion was met. All enrolled patients who received ≥ 1 dose of romidepsin were included in the AE analyses.ResultsOverall, safety profiles of common AEs were similar, although patients with relapsed/refractory PTCL had more frequent hematologic toxicities and grade ≥ 3 infections. In both patient populations, the greatest incidence of grade ≥ 3 AEs and the majority of discontinuations due to AEs occurred during cycles 1-2. Early discontinuations were primarily related to infection, thrombocytopenia, or electrocardiogram abnormalities, confirming the need to closely monitor patients with poor bone marrow reserve or other comorbidities. Despite this, 28% of patients with relapsed/refractory PTCL and 36% of patients with relapsed/refractory CTCL continued on romidepsin treatment for ≥ 6 cycles.ConclusionsThis study demonstrates that patients with relapsed/refractory PTCL or CTCL have similar AE profiles with romidepsin treatment, although patients with PTCL experienced more frequent and more severe hematologic toxicities and more frequent grade ≥ 3 infections. The greatest incidence of grade ≥ 3 AEs and the majority of discontinuations due to AEs occurred during treatment cycles 1-2. Extended dosing of romidepsin can be tolerated in responding patients.Trial registrationNCT00426764,NCT00106431.

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Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma.

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