A Prospective Study of Rituximab/Bendamustine and Rituximab/DHAP +/- Zanubrutinib Induction Therapy with or without ASCT in Young Newly Diagnosed Mantle Cell Lymphoma
Authors: Wang Hui , Xing Lijie , Liu Dan , Wei Haichen , Lu Ke , He Qiang , Xie Linna , Ma Ji , Qiu Lugui , Li Zengjun 
Published: December 2024

Background: Mantle cell lymphoma (MCL) is an incurable B-cell lymphoma with heterogeneous clinical presentation. MCL is characterised by a poor long-term prognosis. Alternating R-CHOP and R-DHAP (rituximab plus dexamethasone, high-dose cytarabine, and cisplatin) followed by a high-dose cytarabine-containing conditioning regimen and ASCT should be considered standard of care in patients aged 65 years or younger. In elderly MCL, the BRIGHT and STiL trials have confirmed that the rituximab/bendamustine (BR) was superior to the R-CHOP. Single-agent zanubrutinib showed favorable response rate and superior safety in relapsed/refractory (R/R) MCL patients. So, we aimed to investigate the efficacy and safety of alternating BR and R-DHAP +/- zanubrutinib therapy with or without autologous stem cell transplantation (ASCT) in patients aged 65 years or younger with newly diagnosed MCL.

Aims: This study aimed to analyze the efficacy and safety of alternating BR or R-DHAP +/- zanubrutinib therapy with or without ASCT in young newly diagnosed MCL patients.

Methods: Patients with young newly diagnosed MCL were enrolled in this study. Patients received alternating BR and R-DHAP +/- zanubrutinib (160 mg twice daily) as induction therapy, and then received ASCT consolidation therapy or not. The primary endpoints were overall response rate (ORR) and complete response rate (CRR). The secondary endpoints were 2-year overall survival (OS), 2-year progression free survival (PFS) and safety profiles.

Results: Overall, 19 patients by now were enrolled in the study, with baseline characteristics of cohort as follows. Male/female were 16 and 3 respectively. Median age was 57 years (range 40-64), 84.2% had ECOG 0-1, and 18.8% ECOG 2. Most patients were in stage 3 and stage 4 (94.8%). Bone marrow was involved in 15/19 (78.9%) patients. Eighteen patients had classic morphology while one was pleomorphic. In patient cohort, 57.9% (11/19) patients had high Ki-67% and 42.1% (8/19) patients had a low Ki-67% (&lt;30%). Simplified MIPI risk stratification included: low (n=9), intermediate (n=6) and high risk (n=4). TP53 aberration status (mutations or deletion) was available in 10/19 patients and 5 patients had aberrant TP53. Sixteen (16/19) patients also received zanubrutinib. Autologous peripheral blood stem cells were collected in 10 patients, and eight patients received ASCT. Till the date of July 20, 2024, a total of 94.7% (18/19) completed 4 cycles induction therapy. Overall response was 83.3% (15/18), with 61.1% (11/18) complete response (CR) and 22.2% (4/18) partial remission (PR). The end-of-induction ORR and CRR were 75.0% (12/16) and 75.0% (12/16), respectively. Progression during induction occurred in 4 patients, 3 of them had aberrant TP53 and all received zanubrutinib treatment. After a median follow-up of 18.5 months, 2-year PFS and OS were 71.8% and 73.7%, and the median OS and PFS were not reached. During induction immunochemotherapy, grade 3 or 4 adverse events included neutropenia (81%), febrile neutropenia (11%), thrombocytopenia (72%), anemia (28%) and lymphopenia (89%). During the whole treatment, 1 case dided of COVID-19-related pneumonia. No atrial fibrillation and bleeding were observed.

Conclusions: This prospective study demonstrated a favorable efficacy and tolerable safety of alternating BR and R-DHAP +/- zanubrutinib in young newly diagnosed MCL patients, especially in those P53 intact patients.

Keywords: Mantle cell lymphoma; BR; R-DHAP; Zanubrutinib; Autologous stem cell transplantation