ATEZOLIZUMAB + OBINUTUZUMAB + VENETOCLAX IN PATIENTS WITH RELAPSED OR REFRACTORY MARGINAL ZONE LYMPHOMA: PRIMARY ANALYSIS OF A PHASE 2 TRIAL FROM LYSA (2021)

Introduction: Relapsed and refractory (R/R) Marginal Zone Lymphomas (MZL) treatment remains challenging. Atezolizumab (ATE) and obinutuzumab (OBI) are monoclonal antibodies acting respectively to inhibit T-lymphocyte exhaustion or by inducing lymphoma cells cytotoxicity, whereas venetoclax (VEN) is a small molecule inhibiting BCL-2. Combining tumor-targeted therapies with agents that enhance anti-tumor immunity represents an attractive treatment paradigm. This LYSA sponsored multicenter phase 2 trial (NCT03276468) evaluated ATE, OBI and VEN combination in R/R B-cell lymphomas. Herein, we present primary efficacy and safety data from the MZL cohort. Methods: Patients ≥18 years with biopsy-confirmed R/R MZL who failed at least one line of therapy were eligible. OBI was given IV at 1 g on day (D) 1, 8 and 15 of cycle (C) 1 and on D1 from C2 to C8 every 3 weeks. ATE was given IV, 1.2 g every 3 weeks, started at D2 of C1, then administered at D2 of each cycle for 24 cycles. VEN was given orally at 800 mg/D at full dose, starting on D8C1 for 24 cycles. The primary endpoint was the Overall Response Rate (ORR) evaluated by Cheson criteria (CT scan) at the end of induction (EOI) after 8 cycles of ATE, OBI and VEN (M6) or at premature treatment discontinuation. Results: At the time of the primary analysis (08 Jan 2021), 20 MZL patients were enrolled, including 13 nodal MZL, 5 extra-nodal MZL (MALT) and 2 splenic MZL. The median follow-up was 11.9 months [0.7-23.6]. Thirteen patients completed induction phase and 11 patients started maintenance. Baseline characteristics were: median age, 69 years (52-83); male, 55.6%; Ann Arbor Stage IV, 100%; bone marrow infiltration, 38.9%; ≥ 2 extra-nodal sites, 50%; >2 prior lines of therapy, 22.2%; refractory to last line of prior regimen, 33.3%. The ORR at EOI was measured at 66.76% [44.6%-84.4%], including 16.7% of CR and 50.0% PR. Best of radiological response rate (BOR) was 77.8% [56.1%-92.0%] including 22.2% of CR. To date, these responses seem durable with only 3 reported relapses. Eleven patients (55%) received the full induction treatment. At the time of analysis, a median of 8 cycles [1-8] has been administered. A total of 14 (70%) pts experienced grade 3–4 adverse event (AE) and no patient experience an AE that led to discontinuation of any drug. AE of grade 3 or more reported in at least 10% of patients were neutropenia (55.0%), thrombocytopenia (20.0%) and anemia (10.0%). Of note, no patient experienced immune-related disorder during induction. Conclusion: ATE, OBI and VEN combo appears to be well tolerated, with no unexpected toxicity brought by the combination. The ORR at EOI seems to be comparable to other innovative regiments in this setting, with durable responses to date. The research was funded by: Roche, Abbvie Keywords: Extranodal non-Hodgkin lymphoma, Indolent non-Hodgkin lymphoma, Combination Therapies Conflicts of interests pertinent to the abstract C. Herbaux Consultant or advisory role: Roche, Abbvie Honoraria: Roche, Abbvie Educational grants: Roche, Abbvie