Mantle cell lymphoma (MCL) is a medium- or small-B-cell lymphoma originating from the mantle zone of lymph node follicles, accounting for about 4.6% of B-cell non-Hodgkin lymphomas (NHL). The median age of onset for MCL is 65 years, with a higher incidence in males, with a male-to-female ratio of approximately 2-4:1. MCL can be categorized into classical MCL, non-nodal leukemic MCL, and in situ mantle cell neoplasia (ISMCN). MCL is characterized by the aggressiveness of aggressive lymphomas and the incurability of indolent lymphomas, leading to a generally poor prognosis. From June 13-16, 2024, the 29th Annual Meeting of the European Hematology Association (EHA) was held in Madrid, Spain. A study by Professor Qingqing Cai's team from Sun Yat-sen University Cancer Center was selected for poster presentation (P1148), offering a new "reduced chemotherapy" treatment strategy for newly diagnosed MCL patients. This article provides a detailed overview of the study for our readers.

Abstract: P1148

Phase II CHESS Study Results of Zanubrutinib Combined with Rituximab (ZR) Sequential Short-Course R-DHAOx Regimen as First-Line Treatment for Mantle Cell Lymphoma (MCL) Lead Author: Professor Qingqing Cai, Sun Yat-sen University Cancer Center

Research Background

BTK inhibitors combined with rituximab have shown good efficacy as first-line treatments for mantle cell lymphoma (MCL). Zanubrutinib, a new generation, highly selective BTK inhibitor, has demonstrated encouraging antitumor activity in MCL.

Research Objective

This multicenter phase II clinical study (CHESS – Chemotherapy-Free) aims to explore the efficacy and toxicity of zanubrutinib combined with rituximab (ZR) sequential short-course chemotherapy based on cytarabine, followed by zanubrutinib maintenance therapy as a first-line treatment for MCL (NCT04624958).

Research Methods

Previously untreated MCL patients were included to receive ZR induction therapy until complete remission (CR) or up to 12 cycles, followed by four cycles of the R-DHAOx regimen (rituximab, dexamethasone, cytarabine, and oxaliplatin). Patients achieving CR after chemotherapy received up to one year of zanubrutinib maintenance therapy. The primary endpoint was the CR rate after ZR induction therapy. Minimal residual disease (MRD) in bone marrow and peripheral blood was assessed by flow cytometry.

Research Results

From October 2020 to November 2023, 42 patients were recruited with a median age of 57 years (IQR, 51-64 years). Stage III-IV patients accounted for 92.8%, with 42.8% of patients having intermediate or high-risk simplified MIPI scores. Thirty-four patients (81.0%) had classical MCL. The median number of ZR treatment cycles was four (range, 2-6). As of January 2024, among 37/42 patients who completed treatment and underwent PET evaluation, the best CR rate for the ZR regimen was 91.9% (34/37), with 94.1% (32/34) achieving CR after 2-4 cycles. The bone marrow MRD-negative CR rate was 92.0% (23/25). The other five patients were still receiving ZR treatment and awaiting PET evaluation. Among 27 patients who completed chemotherapy and were evaluable for efficacy, only one patient experienced disease progression. With a median follow-up time of 11.6 months, the 1-year PFS and OS rates were 90.1% and 96.7%, respectively. Two patients died, one from lymphoma and one from COVID-19. Grade 3-4 adverse events (AEs) in the ZR regimen included neutropenia (n=3), fatigue (n=2), and elevated transaminases (n=1). During chemotherapy, 75.8% of patients experienced grade 3-4 thrombocytopenia.

Research Conclusion

ZR induction therapy followed by short-term R-DHAOx chemotherapy achieved encouraging antitumor efficacy. This strategy may reduce the toxicity of cytarabine-based chemotherapy without compromising treatment effectiveness.