Abstract

Concurrent administration pembrolizumab with chemotherapy in untreated classical Hodgkin lymphoma (CHL) has not previously been studied. To investigate this combination, we conducted a single arm study of concurrent pembrolizumab with AVD (APVD) for untreated CHL. We enrolled 30 patients (6 early favorable, 6 early unfavorable, and 18 advanced stage, median age 33 years (range 18-69 years)) and met the primary safety endpoint with no observed significant treatment delays in the first two cycles. Twelve patients experienced grade 3-4 non-hematologic adverse events (AEs) most commonly febrile neutropenia (5, 17%) and infection/sepsis (3, 10%). Grade 3-4 immune-related AEs were seen in 3 patients, including ALT elevation (3, 10%) and AST elevation (1, 3%). One patient experienced an episode of grade 2 colitis and arthritis. Six (20%) patients missed at least one dose of pembrolizumab due to adverse events, primarily grade 2 or higher transaminitis (5, 17%). Among 29 response-evaluable patients, the best overall response rate was 100% and CR rate of 90%. With median follow up of 2.1 years, 2-year progression-free survival (PFS) and overall survival were 97% and 100%, respectively. To date, no patient who withheld or discontinued pembrolizumab due to toxicity has progressed. Clearance of ctDNA was associated with superior PFS when measured after cycle 2 (p=0.025) and at end of treatment (EOT, p=0.0016). None of the 4 patients with persistent disease by FDG-PET at EOT yet negative ctDNA have relapsed to date. Concurrent APVD shows promising safety and efficacy, but may yield spurious PET findings in some patients. Trial Registration Number: NCT03331341.

View details for DOI 10.1182/blood.2022019254

View details for PubMedID 36913694