Pembrolizumab Approved by EU for Hodgkin Lymphoma

Pier Luigi Zinzani, MD, PhD

Pier Luigi Zinzani, MD, PhD

Pembrolizumab (Keytruda) has been approved by the European Commission (EC) for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL) who have progressed following autologous stem cell transplant (ASCT) and brentuximab vedotin (Adcetris), or who are transplant-ineligible and have failed brentuximab vedotin.

The approval is based on results from the phase II KEYNOTE-087¹and phase Ib KEYNOTE-013²trials. In KEYNOTE-087, at a median follow-up of 9.4 months, the overall response rate (ORR) with the PD-1 inhibitor pembrolizumab was 69% (95% CI, 62-75). The ORR included complete responses (CRs) in 22% of patients and partial responses (PRs) in 47% of patients. The median duration of response was 11.1 months (range, 0+ to 11.1) among the 145 responding patients.

The EC action follows a recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use issued in March. Pembrolizumab is now approved for this indication in all 28 European Union member states plus Iceland, Lichtenstein, and Norway

“For patients with classical Hodgkin lymphoma who have not been successfully treated with prior therapies—many of whom are young and have a poor prognosis—there are limited options and treating the disease poses significant challenges,” said Pier Luigi Zinzani, MD, PhD, associate professor of hematology, Institute of Hematology “L. e A. Seràgnoli,” University of Bologna. “With this approval, we will now be able to provide these patients with a much-needed new treatment option.”

The KEYNOTE-087 trial included 210 adult patients with relapsed/refractory cHL. The median age was 35 (range, 18-76) and 9% of patients were older than 65. Fifty-four percent of patients were male and 88% were white. The ECOG performance status was 0 for 49% of patients and 1 for 51% of patients.

The median number of prior therapies was 4 (range, 1-12) and 58% of patients were refractory to their last prior therapy, including 35% with primary refractory disease and 14% with cHL that was chemorefractory to all prior regimens. Prior treatment included autologous hematopoietic stem cell transplantation (61%), brentuximab vedotin (83%), and radiation therapy (36%).

Pembrolizumab was administered at 200 mg every 3 weeks until disease progression, unacceptable toxicity, or up to 2 years in patients who did not progress. Patients were assessed every 12 weeks to determine the status of their disease.

In the KEYNOTE-013 study, 31 patients received pembrolizumab at 10 mg/kg every 2 weeks for up to 2 years. Sixty-eight percent of patients had received ≥4 prior lines of therapy and 71% had failed prior ASCT. All patients had progressed on prior brentuximab vedotin.

The ORR of 64.5% (20/31) included 5 CRs (16.1%) and 15 PRs (48.4%). Additionally, 23% of patients experienced stable disease with pembrolizumab. After a median of 9.7 months of follow-up, median duration of response was not yet reached (range, 0-13.4+ months), with most responses (n = 14) ongoing at the time of the analysis. At the data cutoff, 45% of patients remained on therapy.

For the cHL approval, the EC evaluated safety data from 3194 patients with advanced melanoma, non—small cell lung cancer, or cHL enrolled in various clinical trials who received pembrolizumab at 1 of 4 doses: 2 mg/kg every 3 weeks; 200 mg every 3 weeks; or 10 mg/kg every 2 or 3 weeks. All-grade adverse events (AEs) occurring in at least 10% of patients included fatigue (22%), pruritus (15%), rash (13%), diarrhea (12%), and nausea (10%). Immune-related adverse reactions and severe infusion-related reactions were the most serious AEs reported.

“Today’s approval brings an important new treatment option to patients in Europe with classical Hodgkin lymphoma who have not responded to existing therapies,” Roger Dansey, MD, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories, the manufacturer of pembrolizumab, said in a statement. “This milestone underscores our commitment to evaluating Keytruda in diseases with unmet need facing the hematology community.”

References:

1. Chen RW, Zinzani PL, Fanale MA, et al. Pembrolizumab for relapsed/refractory classical Hodgkin lymphoma (R/R cHL): phase 2 KEYNOTE-087 study.JClin Oncol34, 2016 (suppl; abstr 7555).
2. Armand P, Shipp MA, Ribrag V, et al. PD-1 blockade with pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure: safety, efficacy, and biomarker assessment. Presented at: 57th American Society of Hematology Annual Meeting; Orlando, Florida; December 5-8, 2015. Abstract 680.