FROM THE JOURNAL OF CLINICAL ONCOLOGY
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.
More than two-thirds of the 210 patients in the phase II trial who were given pembrolizumab – an antibody that blocks interaction of programmed death 1 with its ligands – had a partial or complete response (J Clin Oncol. 2017 Apr 25. doi: 10.1200/JCO.2016.72.1316 ). The safety profile was as expected from past experience with this agent.
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.
