PEMBROLIZUMAB MONOTHERAPY IN PATIENTS WITH PRIMARY REFRACTORY CLASSICAL HODGKIN LYMPHOMA: SUBGROUP ANALYSIS OF THE PHASE 2 KEYNOTE‐087 STUDY

Abstract

Introduction: Patients (pts) with primary refractory classical Hodgkin lymphoma (cHL) have poorer outcomes compared with those who respond to first-line therapy (Shah et al. Br J Haematol. 2016;175:440-447). The PD-1 inhibitor pembrolizumab (pembro) has shown robust antitumor activity (ORR = 69%) and acceptable safety in pts with relapsed or refractory (R/R) cHL in the KEYNOTE-087 study (Chen et al. J Clin Oncol. 2017, in press). As the MOA of pembro is fundamentally different from that of chemotherapy, it may also have important activity in the high-risk subset of pts with primary chemorefractory disease. Presented here is efficacy and safety of pembro in the primary refractory subgroup of KEYNOTE-087. Methods: This phase 2, multicenter, single-arm, multicohort study (NCT02453594) investigated the safety and efficacy of pembro in pts with R/R cHL. Pts received pembro 200 mg IV Q3W. Response was assessed every 12 weeks per 2007 Revised Response Criteria for Malignant Lymphomas. ORR was assessed by blinded independent central review. Here, efficacy and safety were analyzed post hoc in the pt subset with primary refractory cHL (no documented CR with firstline treatment). Results: of 210 pts treated, 73 (34.8%) had primary refractory cHL. Median (range) age was 31.0 (18-73) y. Pts received a median (range) of 3.0 (1.0-12.0) prior lines of therapy; 65 (89.0%) had ≥3 lines of prior therapy; 63 (86.3%) had received prior brentuximab vedotin. ORR was 79.5% (n = 58; 95% CI, 68.4%-88.0%); CR rate was 23.3% (n = 17; 95% CI, 14.2%-34.6%), and PR rate was 56.2% (n = 41; 95% CI, 44.1%-67.8%). SD rate was 5.5% (n = 4; 95% CI, 1.5%-13.4%), and PD rate was 11.0% (n = 8; 95% CI, 4.9%-20.5%). Median (range) time to response was 2.8 (2.1-8.8) mo, and median response duration was not reached. At 6 months, the PFS and OS rates were 79.6% and 100%, respectively. At database cutoff of Sept 25, 2016, 30 pts discontinued treatment, mainly because of progressive disease (n = 10; 13.7%) and physician decision (n = 8; 11.0%). Median (range) duration of follow-up was 10.1 (6.4-14.9) mo. Treatment-related adverse events (TRAEs) occurred in 46 (63.0%) pts and were consistent with the established safety profile of pembro. 4 pts experienced grade 3 TRAEs, and 2 had grade 4 TRAEs. There were no deaths due to TRAEs. TRAEs led to study discontinuation in 3 pts (myocarditis, cytokine release syndrome, infusion-related reaction, and pneumonitis). of 59 pts with adequate pretreatment tumor tissue, all were PD-L1+; 35 had maximum PD-L1 scores that emphasized staining intensity, histiocytes, and membrane staining. Updated data with additional follow-up will be presented. Conclusions: Pembro activity in the KEYNOTE-087 pt subgroup with primary refractory disease appeared comparable with that of the overall R/R cHL population. Pembro may be an effective treatment option for pts with primary refractory cHL, who urgently need new treatment options.