FDA approves Keytruda for relapsed, refractory classical Hodgkin lymphoma

The FDA approved pembrolizumab for adults and children with classical Hodgkin lymphoma who are refractory to treatment or who have relapsed after three or more prior lines of therapy, according to the drug’s manufacturer.

Pembrolizumab (Keytruda, Merck) is the only anti–PD-1 therapy approved for the treatment of classical Hodgkin lymphoma regardless of prior hematopoietic stem cell transplantation or therapy with brentuximab vedotin (Adcetris, Seattle Genetics).

The approval is based, in part, on data from the KEYNOTE-087 trial, which included 210 patients who received 200 mg pembrolizumab every 3 weeks. Fifty-eight percent of patients were refractory to their last therapy, including 35% who had primary refractory disease and 14% whose disease was chemotherapy refractory to all prior regimens. Sixty-one percent of patients had undergone prior HSCT, 17% had no prior brentuximab use and 36% had prior radiation therapy.

Median follow-up was 9.4 months. Results showed an ORR of 69% (95% CI, 62-75), which included a complete remission rate of 22% and a partial remission rate of 47%.

Median duration of response among the 145 responders was 11.1 months (range, 0+ to 11.1).

“The results from KEYNOTE-087 showed that most patients with relapsed or refractory classical Hodgkin lymphoma responded to treatment with Keytruda, and 22% experienced complete remission,” Roger M. Perlmutter, MD, PhD, president of Merck Research Laboratories, said in a company-issued press release. “Today’s approval — the first for Keytruda in a hematologic malignancy — reinforces the hope that immunotherapy will prove useful in a wide variety of cancers.”

Five percent of patients discontinued therapy due to adverse events and 26% experienced treatment interruption. Fifteen percent of patients had an adverse event that required systemic corticosteroid therapy. The most common adverse events included fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%) and rash (20%).

Serious adverse events occurred in 16% of patients, the most frequent of which included pneumonia, pneumonitis, pyrexia, dyspnea, graft-versus-hosts disease (GVHD) and herpes zoster. Two patients died of causes other than disease progression: one of GVHD after subsequent allogeneic HSCT and one of septic shock.

Data on pediatric patients are limited and efficacy was extrapolated from the results in the adult trial. In another study, 40 children with advanced melanoma; PD-L1–positive advanced, relapsed or refractory solid tumors; or lymphoma received pembrolizumab for a median of 43 days (range, 1-414 days), with 24 patients (60%) receiving treatment for 42 days or more.

The drug’s safety profile appeared comparable among adults and children. Toxicities that occurred at a 15% or greater rate in children than adults included fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%) and hyponatremia (18%).

“For the patients with classical Hodgkin lymphoma who are not cured with existing treatments, there are limited options, and treating their disease becomes more challenging,” Craig H. Moskowitz, MD, clinical director in the division of hematologic oncology at Memorial Sloan Kettering Cancer Center and a HemOnc Today Editorial Board member, said in the release. “This approval is an important step forward in treating these patients, who are generally young and have a particularly poor prognosis, and gives us the opportunity to help patients in their fight against this devastating disease.”

March 14, 2017 Healio.com