Frontline treatment with zanubrutinib plus rituximab (ZR) followed by short course R-DHAOx in patients with mantle cell lymphoma (MCL): Results of the phase II CHESS clinical trial.

7062 Background: Combining Bruton’s tyrosine kinase (BTK) inhibitor and rituximab showed favourable efficacy as first-line therapy for mantle cell lymphoma (MCL). Zanubrutinib, a next-generation, highly-selective BTK inhibitor, achieved promising antitumor activity in MCL. In this multicenter phase II trial (CHESS - chemo-less), we aimed to investigate the efficacy and toxicity of zanubrutinib plus rituximab (ZR) combination, followed by short course cytarabine-based chemotherapy, then zanubrutinib maintenance as frontline therapy for MCL (NCT04624958). Methods: Previously untreated MCL patients enrolled and received induction therapy of ZR until complete response (CR) or to a maximum of 12 cycles, and followed by 4 cycles of R-DHAOx regimen (rituximab, dexamethasone, cytarabine and oxaliplatin). Patients achieving CR after chemotherapy would receive maintenance therapy with zanubrutinib for a maximum of 1 year. The primary endpoint was CR rate after induction therapy with ZR regimen. Minimal residual disease (MRD) of bone marrow and peripheral blood were evaluated by flow cytometry. Results: From Oct 2020 to Nov 2023, a total of 42 patients were enrolled and the enrollment was finished. The median age was 57 years (IQR, 51-64). Stage III-IV accounted for 92.8%, and 42.8% were intermediate or high risk simplified MIPI. Thirty-four patients (81.0%) were classic histological subtype. The median cycle of ZR was 4 (range, 2-6). As of Jan 2024, among 37/42 patients with post-treatment PET evaluation, the best CR rate of ZR regimen was 91.9% (34/37), and 94.1% (32/34) obtained CR after 2-4 cycles. The bone marrow MRD negative CR rate was 92.0% (23/25). The other 5/42 patients were still receiving ZR treatment, and PET evaluation would be performed subsequently. Among 27 patients who finished chemotherapy and were evaluable for response, only one patient experienced disease progression. With a median follow up of 11.6 months, the 1-year progression-free survival and overall survival was 90.1% and 96.7%, respectively. Two patients died due to lymphoma (n=1) and COVID-19 (n=1). Grade 3-4 adverse events on ZR regimen were neutropenia (n=3), fatigue (n=2), and aminotransferase (n=1). During chemotherapy, grade 3-4 thrombocytopenia was observed in 75.8% of patients. Conclusions: Induction treatment with ZR followed by short-course R-DHAOx chemotherapy yielded promising antitumor efficacy. This strategy might reduce the toxicity of cytarabine-based chemotherapy without weakening the therapeutic efficacy. Clinical trial information: NCT04624958 . Table: see text