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.