Pembrolizumab has been granted an accelerated approval by the FDA for the treatment of adult and pediatric patients with classical Hodgkin lymphoma who are refractory or have relapsed after 3 or more lines of therapy.
Pembrolizumab (Keytruda) has been granted an accelerated approval by the FDA for the treatment of adult and pediatric patients with classical Hodgkin lymphoma (cHL) who are refractory or have relapsed after 3 or more lines of therapy.
The approval is based on data from a nonrandomized, open-label clinical trial in which, at a median follow-up of 9.4 months, the overall response rate (ORR) with pembrolizumab was 69% (95% CI, 62-75). The ORR included complete responses in 22% of patients and partial responses in 47% of patients. The median duration of response was 11.1 months (range, 0+ to 11.1).
The specific pembrolizumab regimens approved are 200 mg every 3 weeks for adults and 2 mg/kg (up to 200 mg) every 3 weeks for pediatric patients. This is the first FDA indication for pembrolizumab in a hematologic malignancy.
The pivotal multicenter study of pembrolizumab enrolled 210 adult patients with relapsed/refractory cHL. Of the overall population, 129 patients had received autologous stem cell transplantation and 175 patients had received brentuximab vedotin (Adcetris). The median number of prior therapies was 4 (range, 1-12).
The most common adverse events (≥20% of patients) included fatigue, pyrexia, cough, musculoskeletal pain, diarrhea, rash and hypertransaminasemia. Adverse events occurring in at least 10% of patients included dyspnea, arthralgia, vomiting, nausea, pruritus, hypothyroidism, upper respiratory tract infections, headache, peripheral neuropathy, hyperbilirubinemia and increased creatinine.
Additional immune-mediated adverse reactions occurring in 0.5% to 9% of patients included infusion reactions, hyperthyroidism, pneumonitis, uveitis, myositis, myelitis and myocarditis. Adverse events requiring corticosteroid therapy occurred in 15% of patients. Adverse reactions led to discontinuations and treatment interruptions in 5% and 26% of patients, respectively.
The FDA also considered safety data for 40 children with advanced melanoma, PD-L1­positive solid tumors, or lymphoma. The safety profile in the pediatric patients was consistent to that observed in adults. Some adverse events occurred at a higher rate (≥15% difference) in children than in adults, including fatigue, vomiting, abdominal pain, hypertransaminasemia and hyponatremia. Pembrolizumab exposure at a dose of 2 mg/kg every 3 weeks in these pediatric patients was comparable to that observed in adults.
Pembrolizumab’s label has also been updated with a new "Warning and Precaution" for complications of allogeneic hematopoietic stem cell transplantation after treatment with the PD-1 inhibitor. The warning informs healthcare professionals to monitor patients closely for early signals of transplant-related complications, such as hyperacute GVHD, grade 3/4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions.
The acclerated approval of pembrolizumab in cHL is contingent upon the results of a confirmatory trial verifying the benefit of the PD-1 inhibitor in this setting.