Clinical Benefit Observed with Pembrolizumab in Heavily Pretreated Classical Hodgkin Lymphoma

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Patients with classical Hodgkin lymphoma who were heavily pretreated had clinical benefit from pembrolizumab.
Patients with classical Hodgkin lymphoma who were heavily pretreated had clinical benefit from pembrolizumab.

SAN FRANCISCO—Patients with classical Hodgkin lymphoma (cHL) who were heavily pretreated—including those who had failed brentuximab vedotin—had clinical benefit from pembrolizumab (MK-3475), according to preliminary results from a open-label phase 1b study (Abstract 290) reported at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition.

In 29 of the 31 patients in the KEYNOTE-013 study evaluable for response, the clinical benefit rate was 86%, and the overall response rate was 66%, which included 6 (21%) complete remissions, said Craig H. Moskowitz, MD, of the Department of Medicine, Memorial Sloan Kettering Cancer Center in New York, NY. In addition, pembrolizumab, which blocks the programmed death-1 (PD-1) pathway, was well tolerated.

These results “support the continued development of pembrolizumab in patients with Hodgkin lymphoma,” Dr. Moskowitz said. Among the enrolled patients, PD-L1 expression was observed in 100% of the evaluable samples.

Median age of the patients was 32 years (range, 20-67 years); 52% of patients had received 5 or more prior therapies for advanced disease. In addition to failing brentuximab vedotin, 69% of patients had also failed autologous stem cell transplantation.

At the analysis cut-off date of November 17, 2014, median time to response was 12 weeks; 17 of 19 (89%) of patients had responses that were ongoing. Median duration of response was not reached (range, 1+ to 185+ days). At a median duration of follow-up of 153 days (range, 1-341), 9 patients had discontinued therapy, 1 due to an adverse event, 7 due to disease progression, and 1 due to a complete response. Twenty patients remained on therapy and 1 patient went on to transplant.

Three patients (10%) experienced a total of 4 adverse events that were grade 3; no grade 4 treatment-related AEs or treatment-related deaths were observed. The grade 3 adverse events (AEs) were one occurrence each of axillary pain, hypoxia, joint swelling, and pneumonitis.

The AEs of clinical interest included hyperthyroidism (grade 1-2 in 2 patients), hypothyroidism (grade 1-2 in 3 patients), pneumonitis (grade 1-2 in 2 patients and grade 3 in 1 patient), and colitis in 2 patients (grade 3 in 1 patient and not reported in 1 patient).

“It will be important to further evaluate this drug in combination with others, or perhaps even as a maintenance treatment, to enhance the post-transplant immune response,” Dr. Moskowitz said in a press release.

Reference
  1. Moskowitz, Craig H., MD, et al. "290 PD-1 Blockade with the Monoclonal Antibody Pembrolizumab (MK-3475) in Patients with Classical Hodgkin Lymphoma after Brentuximab Vedotin Failure: Preliminary Results from a Phase 1b Study (KEYNOTE-013)." ASH 2014. Oral Presentation. December 8, 2014.

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