On 14 March 2017, the programmed death receptor 1 (PD-1) inhibitor pembrolizumab (Keytruda®, Merck) received accelerated approval from the United States Food and Drug Administration (FDA) for the treatment of adult and pediatric patients with classical Hodgkin lymphoma who are refractory or have relapsed after three or more lines of therapy.
Pembrolizumab is the second PD-1 inhibitor approved for this indication; nivolumab was approved in May 2016 on the basis of two phase II single arm trials in adult patients (the CheckMate-205 trial and the CheckMate-039 trial).
Pembrolizumab’s approval is based on results from the nonrandomized open-label Keynote-087 trial, which evaluated pembrolizumab (200 mg every three weeks) in 210 adult patients with relapsed or refractory disease after autologous stem cell transplant and/or brentuximab vedotin. At a median follow-up of 9.4 months, pembrolizumab treatment resulted in an overall response rate of 69%, including complete response in 22% of patients. The estimated median duration of response was 11.1 months. Efficacy in pediatric patients was extrapolated from results in adults.
Safety was evaluated in 210 adult patients with Hodgkin lymphoma. The most common adverse events (AEs) included fatigue (26%), pyrexia and cough (24% each), musculoskeletal pain (21%), and diarrhea and rash (20% each). Fifteen percent of patients required systemic corticosteroids due to AEs. For pediatric patients, safety was extrapolated from 40 pediatric patients with melanoma, solid tumors, or lymphoma. The safety profile in these patients was consistent with that observed in adults, with the exception that fatigue, vomiting, abdominal pain, hypertransaminasemia, and hyponatremia occurred at higher rates (≥15% difference) in children than adults.
Pembrolizumab will be given at a dose of 2 mg/kg every 3 weeks in children and 200 mg every 3 weeks flat dose in adults. It will carry a warning about the risk of transplant-related deaths in patients receiving allogeneic hematopoietic stem cell transplant following pembrolizumab. Physicians are advised to follow these patients closely for the risk of complications including graft versus host disease, hematologic vascular occlusive disease, and other immune-mediated adverse reactions.