Keytruda Granted FDA Approval for Hodgkin Lymphoma

Keytruda (pembrolizumab) was granted an accelerated approval by the Food and Drug Administration (FDA) for the treatment of refractory or relapsed adult and pediatric patients with classical Hodgkin lymphoma (cHL) who have had three 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 Keytruda was 69 percent. The ORR included complete responses in 22 percent of patients and partial responses in 47 percent of patients. The median duration of response was 11.1 months (range, 0+ to 11.1).

The specific Keytruda regimens approved are 200 mg every three weeks for adults and 2 mg/kg (up to 200 mg) every three weeks for pediatric patients. This is the first FDA indication for Keytruda in a hematologic malignancy.

The pivotal multicenter study of Keytruda 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 Adcetris (brentuximab vedotin). The median number of prior therapies was four (range, 1-12).

The most common adverse events (20 percent or more of patients) included fatigue, pyrexia, cough, musculoskeletal pain, diarrhea, rash and hypertransaminasemia. Adverse events occurring in at least 10 percent 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 percent to 9 percent of patients included infusion reactions, hyperthyroidism, pneumonitis, uveitis, myositis, myelitis and myocarditis. Adverse events requiring corticosteroid therapy occurred in 15 percent of patients. Adverse reactions led to discontinuations and treatment interruptions in 5 percent and 26 percent of patients, respectively.

The FDA also considered safety data for 40 children with advanced melanoma, PD-L1­—positive 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 percent or more difference) in children than in adults, including fatigue, vomiting, abdominal pain, hypertransaminasemia and hyponatremia. Keytruda exposure at a dose of 2 mg/kg every three weeks in these pediatric patients was comparable to that observed in adults.

Keytruda’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 Keytruda in cHL is contingent upon the results of a confirmatory trial verifying the benefit of the PD-1 inhibitor in this setting.