ISHL10 Abstract T023

Pembrolizumab for relapsed/refractory classical Hodgkin Lymphoma (R/R cHL): Multicohort, phase 2 KEYNOTE-087 study

Background: In the phase 1b KEYNOTE-013 study, PD-1 blockade with pembrolizumab demonstrated high antitumor activity (65% ORR) in heavily pretreated cHL patients. KEYNOTE-087 (NCT02453594) is a phase 2 study designed to further evaluate the clinical activity of pembrolizumab in patients with R/R cHL. Methods: Patients were enrolled into 3 cohorts: R/R cHL after autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV) therapy (cohort 1); ineligible for ASCT because of chemotherapy resistance (no response to salvage chemotherapy) and BV therapy failure (cohort 2); or R/R cHL after ASCT, but not treated with BV after ASCT (cohort 3). Patients received pembrolizumab 200 mg Q3W. Primary end point was ORR, with response assessed Q12W according to Revised Response Criteria for Malignant Lymphoma. A prespecified interim analysis, based on investigator-assessed response, was performed after 30 patients in cohorts 1 and 2 reached the first response assessment. Results: At the time of data cutoff (April 8, 2016), 90 patients were enrolled (30 in each cohort). Median (range) age was 36 (19-64) years in cohort 1, 33 (20-71) years in cohort 2, and 30 (18-67) years in cohort 3. 42% had primary refractory disease (no response to frontline therapy), and 57% received >3 prior lines of therapy. By investigator review, ORR was 73% (95% CI, 54%-88%) in cohorts 1 and 3, and 83% (95% CI, 65%-94%) in cohort 2. Complete remission rates (residual mass permitted if PET negative) were 27% in cohort 1 and 30% in cohorts 2 and 3. With a median of 9 treatment cycles, the most common treatment-related AEs (TRAEs) were pyrexia (13%), diarrhea (10%), and cough, fatigue, and neutropenia (8% each). There were 8 grade 3-4 TRAEs occurring in 4 patients (grade 3 neutropenia, colitis, diarrhea, cytokine release syndrome, herpes zoster infection, increased amylase, lichenoid keratosis, and grade 4 increased lipase). There were no treatment-related deaths. Conclusions: Pembrolizumab showed frequent responses in heavily pretreated patients with cHL, and provided a high ORR (83%) in patients who were not candidates for ASCT and failed previous BV therapy.