P1103: obinutuzumab induction and maintenance in patients with relapsed/refractory waldenström macroglobulinaemia

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Chemoimmunotherapy based on rituximab remains the cornerstone of treating symptomatic patients with Waldenström macroglobulinaemia. Other targeting agents are studied to improve outcomes and evaluate the value of new approaches to treat the disease. Obinutuzumab is a novel, potent, humanized anti-CD20 monoclonal antibody effective in indolent B-cell lymphomas. Aims: The OBI-1 study (EUDRACT, 2016-005053-20) evaluated the efficacy and safety of obinutuzumab induction and maintenance in patients with relapsed or refractory Waldenström macroglobulinaemia. Methods: The OBI-1 was an open-label, phase 2, single-arm study initiated by the Polish Myeloma Consortium and conducted in five Polish hospitals. Eligible patients had measurable, relapsed, or refractory Waldenström macroglobulinaemia with CD20 expression and required treatment according to the 7th International Workshop on Waldenström Macroglobulinaemia (IWWM) criteria. In the induction phase, patients received an intravenous infusion of obinutuzumab 1000 mg on days 1, 8, and 15 in the first 21-day cycle, followed by up to a maximum of five further 21-day cycles with obinutuzumab infusions on day 1. After the induction phase, patients with at least stable disease entered 2-year maintenance treatment with obinutuzumab 1000 mg every eight weeks. The primary endpoint was best overall response (BOR, minor response or better recorded from the start until the end of treatment) as per the 7th IWWM criteria; secondary outcomes included overall response rate (ORR, minor response or better evaluated after the end of induction and maintenance phases), progression-free survival (PFS), overall survival (OS) and safety. Results: After screening 33 patients, 23 were enrolled. The median age was 66 years (range 52-86), and the median number of prior treatments was 1 (range 1 - 5). The median duration of follow-up was 20.7 months (range 0.9 – 44.1). BOR was reported in 65.2% of patients, with 21.7% of patients achieving very good partial response or better. ORR was 52.2% at the end of induction treatment (12 of 23 patients), and 18 patients received maintenance treatment. Five progression-free survival events occurred during induction and three during maintenance treatment. The 18-month PFS and OS were 68% and 90%, respectively. At least one adverse event (AE) of any grade occurred in 95.7% of patients. The most frequent AEs of any grade were infection (60.8%), neutropenia (21.7%) and thrombocytopenia (17.4%). At least one grade ≥3 adverse event (AE) occurred in 69.6% of patients. The most frequent AEs of grade ≥3 were infection (34.8%) and neutropenia (13.0%). Two patients died during the study, including one death due to cardiac insufficiency and one death related to COVID-19. Summary/Conclusion: Our findings suggest that obinutuzumab induction and maintenance may have significant clinical activity in relapsed and refractory Waldenström macroglobulinaemia. Investigated chemotherapy-free induction and maintenance offered prolonged survival with an acceptable toxicity profile that warrants further investigation of obinutuzumab in Waldenström macroglobulinaemia. Keywords: Induction, relapsed/refractory, Waldenstrom’s macroglobulinemia, Maintenance