FDA approves Keytruda for treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL).- Merck Inc.

Merck Inc., announced that the FDA has approved Keytruda, the company’s anti-PD-1 therapy, for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after two or more prior lines of therapy. This indication is approved under the FDA’s accelerated approval regulations based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Keytruda is not recommended for the treatment of patients with PMBCL who require urgent cytoreductive therapy. With this indication, Keytruda becomes the first anti-PD-1 therapy to be approved for the treatment of PMBCL, a type of non-Hodgkin lymphoma. This is the second indication for Keytruda for the treatment of a hematologic malignancy.

The approval was based on data from KEYNOTE-170 a multicenter, open-label, single-arm trial evaluating Keytruda in 53 patients with relapsed or refractory PMBCL. Patients were not eligible for the trial if they had active non-infectious pneumonitis, allogeneic HSCT within the past five years (or greater than 5 years but with symptoms of GVHD), active autoimmune disease, a medical condition that required immunosuppression, or an active infection requiring systemic therapy. Patients received Keytruda 200 mg every three weeks until unacceptable toxicity or documented disease progression, or for up to 24 months for patients who did not progress. Disease assessments were performed every 12 weeks and assessed by blinded independent central review according to the 2007 revised International Working Group criteria. Efficacy was based on overall response rate (ORR) and duration of response (DOR). In KEYNOTE-170, the ORR was 45 percent (95% CI, 32, 60), with a complete response rate (CRR) of 11 percent and a partial response rate of 34 percent. Median DOR, based on 24 patients who responded, was not reached (range, 1.1+ to 19.2+ months). For the 24 responders, the median time to first objective response (complete or partial response) was 2.8 months (range, 2.1 to 8.5 months). Median follow-up time was 9.7 months. Among the 53 patients with PMBCL treated in KEYNOTE-170, Keytruda was discontinued due to adverse reactions in eight percent of patients, and treatment was interrupted due to adverse reactions in 15 percent.