FDA Grants Priority Review to Pembrolizumab for PMBCL

The FDA granted priority review to a supplemental biologics license application for the anti–PD-1 agent pembrolizumab for adult and pediatric patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL).

The decision was based on results from a cohort of the ongoing, non-randomized, international, two-cohort, multicenter, phase II KEYNOTE-170 trial. The study included 29 patients with PMBCL who were transplant-ineligible or whose disease had relapsed after or was refractory to two or more prior lines of therapy.

By April 14, 2017 (data cutoff), 49 patients with relapsed/refractory PMBCL (median age = 33 years; range = 20-61 years) were followed for a median of 10.5 months (range = 0.1-17.7 months). The ORR was 41 percent (95% CI 0.24-0.61) by blinded independent central review and 38 percent by investigator review. This included a 24 percent (n=7) complete response rate and 17 percent (n=5) partial response rate.

The median time to response was 2.8 months (range = 2.4-5.5 months), while the median duration of response was not reached (range = 1.1-13.6 months). Twelve-month overall survival (OS) was 62 percent, and median OS was not reached.

Thirty patients (57%) experienced treatment-related AEs, and 11 (21%) experienced grade 3 or 4 AEs. The most common AEs were neutropenia (n=11), hypothyroidism (n=4), asthenia (n=3), and pyrexia (n=3). Twenty-nine patients discontinued treatment, mostly because of clinical or radiological progression (n=24) or AEs (n=3).

Sources: Merck press release, December 11, 2017; Zinzani PL, Thieblemont C, Melnichenko V, et al. Efficacy and safety of pembrolizumab in relapsed/refractory primary mediastinal large B-cell lymphoma (rrPMBCL): updated analysis of the Keynote-170 phase 2 trial. Abstract #2833. Presented at the 2017 American Society of Hematology Annual Meeting, December 10, 2017; Atlanta, GA.