Combination of the PD‐1 inhibitor Nivolumab and Immunomodulatory Drug Lenalidomide in Relapsed Hodgkin and Large B‐cell Lymphoma: Results from a Phase I/II Study

Introduction: Lenalidomide (len) and nivolumab (nivo) each have single agent activity in relapsed Hodgkin lymphoma (HL) and large B-cell lymphoma (LBCL) with potential for additive or synergistic activity. The immunomodulatory properties of this combination may salvage response to prior adoptive cellular therapy. We conducted a multicenter, open label, phase 1/2 study to determine the recommended phase 2 dose (RP2D) of len and nivo, and to assess the toxicity and preliminary efficacy of the combination in relapsed HL and LBCL. Methods: Adults with relapsed LBCL ineligible for autologous transplant (ASCT) or relapsed HL with ≥2 prior lines of therapy were eligible. Nivo 240 mg IV every 2 weeks for cycles 1–4 (28 day cycle) and 480 mg IV every 4 weeks beginning cycle 5 was given for up to 12 cycles. Len was given days 1–21 according to dose level (DL) and continued until progression. Results: Thirty-six patients signed informed consent and were treated, including 10 in the phase I cohort, 10 in the phase Ib HL cohort, and 16 in the phase II LBCL cohort. Dose limiting toxicity (DLT) occurred in 2/4 patients at DL 1 (len 15 mg) and included grade 3 rash and grade 3 generalized weakness. Six patients were treated at DL -1 (len 10 mg) with no DLT and thus 10 mg len was selected as the RP2D. The most common adverse events (AE) included diarrhea (44%), rash (42%), and hypothyroidism (25%). Grade ≥3 AE included SARS CoV2 infection (11%), fatigue (8%), pulmonary embolism (3%), and Stevens-Johnson Syndrome (SJS) (3%). Baseline characteristics for the phase Ib HL cohort included median age 28.5 (range 19–43), male sex in 9/10 patients, classical HL in 9 and nodular lymphocyte predominant HL in 1, prior brentuximab in 8/10, prior ASCT in 5/10, prior PD-1 inhibitor in 1/10, and a median of 3 prior treatments (range 2–9). The overall response rate (ORR) was 70% including 30% complete response (CR). The median progression free survival (PFS) and overall survival (OS) were not reached (Figure). Two patients completed 12 cycles of nivo and remain on len treatment. In total 6 patients (2 from phase I and 4 from phase 1b) with HL underwent consolidative ASCT (n = 2) or allogeneic transplant (allo-HCT) (n = 4) directly following discontinuation of study treatment, and all 6 remain alive and relapse-free at data cut-off. For the phase 2 LBCL cohort, the median age was 62, 12/16 patients were male, 14/16 had prior CAR-T, and the median prior treatments were 4 (range 2–5). The ORR was 37%, including 12% CR. The median PFS was 2.6 months with a median OS of 12.3 months. Both patients with CR received CAR-T as the prior treatment and responses were ongoing beyond 12 months. Encore Abstract - previously submitted to EHA 2023 The research was funded by: Bristol Myers Squibb Keywords: Aggressive B-cell non-Hodgkin lymphoma, Hodgkin lymphoma, Immunotherapy Conflicts of interests pertinent to the abstract. D. A. Bond Consultant or advisory role: Nurix Therapeutics, Kite/Gilead, SeaGen Research funding: Novartis, Nurix Therapeutics B. Christian Consultant or advisory role: Genentech; Research funding: Genentech, Acerta, Millenium, Bristol-Myers Squibb