HIGH RESPONSE RATES WITH PEMBROLIZUMAB IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH RELAPSED FOLLICULAR LYMPHOMA: INTERIM RESULTS OF AN ON OPEN‐LABEL, PHASE II STUDY

Abstract

Background: Follicular lymphoma (FL) tumors are infiltrated with antitumor T cells, however, their function is impaired by immune checkpoints such as PD-1/PD-ligand pathway. Blocking PD-1 enhances the function of antitumor T cells in FL. In addition, blocking PD-1 on NK cells has been shown to enhance the ADCC effect of NK cells. We reasoned that the combination of pembrolizumab, an anti-PD-1 antibody, and rituximab (R), an anti-CD20 antibody that induces ADCC, is likely to be synergistic through activation of both the innate and adaptive immune systems and result in enhanced clinical activity in FL. Methods: We evaluated pembrolizumab and R in an open-label, non-randomized, single institution, phase II trial (N = 30). Key inclusion criteria included adult (age ≥ 18 years), FL grade 1-3a, ECOG 0-1, in relapse after ≥1 prior therapy and R sensitive disease, defined as a complete (CR) or partial response lasting at least 6 months after most recent R-containing therapy. Patients received R (375 mg/m2 IV) on days 1, 8, 15, and 22 of cycle 1 and pembrolizumab (200 mg IV) q 3 weeks for up to 16 cycles starting on day 2 of cycle 1. Primary endpoint was overall response rate (ORR). Results: 27 patients have initiated therapy, median age 65 (range 42-79), 52% male, 76% had intermediate or high risk FLIPI, 56% met GELF criteria. Median prior therapy =1 (range 1-4). Adverse events (AE) regardless of causality were mild, most grade 1-2. Grade 3 AE's included nausea (N = 2), infusion reaction (N = 2), aseptic meningitis (N = 1), pneumonia (N = 1). Immune-related AEs included grade 2 diarrhea (N = 2), grade 2 pneumonitis (N = 1), grade 2 skin rash (N = 1). At the pre-planned interim analysis (N = 15), ORR was 80%, CR rate was 60%. With a median follow up of 7 months (range 0.5-17), median DOR, PFS, and OS has not been reached. PD-L1 expression was tested in 8 baseline tumor samples using PD-L1 22C3 IHC pharmDx and was detected in histiocytes in all 8 tumors, present in only 1-8% of tumor cells in 5 tumors. Additional biomarker analyses are ongoing. Conclusions: The combination of pembrolizumab and R is well tolerated in relapsed FL and is associated with high overall and CR rate. These interim results warrant further investigation of this combination in FL. Keywords: follicular lymphoma (FL); monoclonal antibodies (MoAb); rituximab.