Keytruda Granted Accelerated Approval for Lymphoma
Pembrolizumab approved for adults and pediatric patients with refractory classical Hodgkin lymphoma.
The FDA granted accelerated approval to pembrolizumab (Keytruda) for the treatment of adults and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior treatments.
The recommended dose and scheduling is 200 mg of pembrolizumab every 3 weeks for adults and 2 mg/kg—–up to 200 mg––every 3 weeks for pediatric patients.
The approval was based on data from a multicenter, open-label, non-randomized clinical trial that included 210 adults with cHL, according to a press release.
Participants had relapsed or refractory disease following an autologous stem cell transplant or treatment with brentuximab vedotin (Adcetris), and had received a median of 4 prior systemic therapies. The median follow-up was 9.4 months.
The results of the study showed that the overall response rate was 69%, which consisted of partial responses in 47% of patients and complete responses in 22% of patients. The estimated median response duration was 11.1 months.
Efficacy in pediatric patients with cHL was extrapolated from the results found in adults, according to the release.
The most common adverse events (AEs) in at least 20% of adults administered pembrolizumab were fatigue, pyrexia, cough, musculoskeletal pain, diarrhea, rash, and hypertransaminasemia. Common AEs in at least 10% of patients were dyspnea, arthralgia, vomiting nausea, pruritus, hypothyroidism, upper respiratory tract infections, headache, peripheral neuropathy, hyperbilirubinemia, and increased creatinine.
Immune-mediated AEs that occurred in 0.5% to 9% of patients included infusion site reactions, hyperthyroidism, pneumonitis, uveitis, myositis, myelitis, and myocarditis.
There were 15% of patients who experienced an AE that required systemic corticosteroid therapy. Pembrolizumab was discontinued in 5% of patients due to AEs, and was interrupted in 26% of patients.
Safety was also evaluated in 40 pediatric patients with advanced melanoma, PD-L1 positive solid tumors, or lymphoma. The safety profile was similar to that observed in adults, according to the release.
AEs occurred at a higher rate that had a difference of 15% or greater in children than adults. AEs included fatigue, vomiting, abdominal pain, hypertransaminasemia, and hyponatremia.
The FDA requires the long-term safety of pembrolizumab to be evaluated in pre-pubertal patients, as well as those who have not completed pubertal development.
Additionally, a new Warning and Precaution has been added for complications of allogenic hematopoietic stem cell transplantation after pembrolizumab.