The immune checkpoint inhibitor pembrolizumab has good antitumor activity and a favorable safety profile when used to treat relapsed or refractory classic Hodgkin lymphoma, according to findings from the KEYNOTE-087 trial.
Pembrolizumab has garnered interest for this population because Hodgkin Reed-Sternberg cells have a chromosomal alteration leading to overexpression of both programmed death ligand 1 and programmed death ligand 2.
Neil Osterweil
Dr. Craig Moskowitz
Programmed death 1 “blockade with pembrolizumab demonstrated substantial clinical activity in subsets of heavily pretreated patients with [classic Hodgkin lymphoma], with most responses observed at the first disease assessment and ongoing at the time of data cutoff,” Craig H. Moskowitz, MD, clinical director of the division of hematologic oncology at the Memorial Sloan-Kettering Cancer Center in New York, and his coinvestigators wrote. Thus, pembrolizumab offers “a new treatment paradigm for this disease.”
The findings have led to initiation of a randomized phase III trial, comparing pembrolizumab with brentuximab vedotin in this population (KEYNOTE-204), they noted.
Patients treated in KEYNOTE-087, a multicenter, single-arm phase II trial supported by Merck, fell into three cohorts, based on the timing of progression. Cohort 1 experienced progression after autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (69 patients); cohort 2 after salvage chemotherapy and brentuximab vedotin, which made them ineligible for ASCT because of chemoresistant disease (81 patients); and cohort 3 after ASCT but without posttransplantation brentuximab vedotin (60 patients).
All patients were treated with pembrolizumab (Keytruda) 200 mg every 3 weeks and underwent response assessment every 12 weeks.
After a median follow-up of 10.1 months (with receipt of a median of 13 treatment cycles), the overall response rate according to central review was 69%, and the complete response rate was 22%, trial results show. At the 6-month mark, overall survival was 99.5% and progression-free survival was 72.4%.
The overall response rate was consistently high across cohorts: 74% for cohort 1, 64% for cohort 2, and 70% for cohort 3. Moreover, 31 patients had a response lasting at least 6 months.
The leading treatment-related adverse events of any grade were hypothyroidism (12%) and fever (11%), and the leading grade 3 or 4 treatment-related adverse events were neutropenia (2%), dyspnea (1%), and diarrhea (1%). Immune-mediated adverse events – most often hypothyroidism – and infusion-related reactions were seen in 29% of patients.
Dr. Moskowitz has ties to Celgene, Genentech, BioOncology, Merck, Pharmacyclics, and Seattle Genetics. The trial was supported by Merck.