Benefit of rituximab maintenance after first-line bendamustine-rituximab in mantle cell lymphoma.
Authors: Wang Yucai , Larson Melissa C. , Kumar Anita , Hill Brian T , Bond David Alan , Kahl Brad S. , Danilov Alexey Valeryevich , Merryman Reid , Grover Natalie Sophia , Tun Aung M. , Ayyappan Sabarish Ram , Pongas Georgios , Portell Craig Anthony , Munoz Javier , Reagan Patrick Michael , Alhaj Moustafa Muhamad , Pophali Priyanka Avinash , Greenwell Irl Brian , Cohen Jonathon Brett , Martin Peter 
Published: June 2024

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Background: Rituximab maintenance (RM) after first-line (1L) bendamustine and rituximab (BR) in MCL did not improve progression-free survival in the MAINTAIN trial (Rummel et al, ASCO 2016) but was associated with improved survival outcomes in a North American observational study (Martin et al, JCO 2023). We sought to examine the potential benefit of RM after BR using a large observational cohort from 26 US academic centers. Methods: Patients with MCL who received 1L BR (without stem cell transplant) outside of clinical trials were included. At the landmark of 3 months after the end of BR, patients who achieved a complete response (CR) or partial response (PR) to BR and had no evidence of progressive disease (PD) or second-line (2L) therapy were deemed eligible for RM. Event-free survival (EFS) was defined as time from landmark to progression, relapse, retreatment, or death. EFS2 was defined as time from landmark to progression, relapse, or retreatment following 2L therapy or death. RM was not considered a line of therapy for either endpoint. OS was defined as time from landmark to death. Survival analysis was done with Kaplan-Meier methods and Cox regression models adjusting for sex and simplified MIPI. Results: Among 796 patients who received 1L BR in 2007-2020, 693 achieved a CR or PR. At the 3-month post-BR landmark, 613 had no evidence of PD, among whom 318 (52%) received RM and 295 did not. The RM group was younger (median age 70 vs 72, p = 0.010) and more predominantly male (78% vs 69%, p = 0.047). There was no statistical difference in stage, simplified MIPI, histology (blastoid or pleomorphic vs classic), Ki-67, TP53 alteration, complex karyotype, year of BR start, or best response to BR between the two groups. The median follow-up after the 3-month post-BR landmark was 61.3 months (95% CI 62.6-70.4). The median number of doses of RM was 10 (IQR 5-12). RM was associated with improved EFS (median 47.1 vs 29.7 months, adjusted HR 0.59, 95% CI 0.48-0.73), EFS2 (median 89.1 vs 48.3 months, adjusted HR 0.63, 95% CI 0.50-0.81), and OS (median 136.1 vs 74.3 months, adjusted HR 0.57, 95% CI 0.44-0.75) (all p values < 0.001). In patients with CR to 1L BR (n=527), 271 (51%) received RM, for a median of 11 (IQR 6-12) doses. In this subgroup, RM was associated with improved EFS (median 60.6 vs 31.5 months, adjusted HR 0.56, 95% CI 0.44-0.71), EFS2 (median 89.1 vs 48.3 months, adjusted HR 0.62, 95% CI 0.48-0.81), and OS (median 136.1 vs 75.6 months, adjusted HR 0.59, 95% CI 0.44-0.79) (all p values < 0.001). Analysis in patients with PR to 1L BR was limited by the sample size (n=86, 47 received RM). The numeric differences in median EFS (20.8 vs 11.5, log-rank p = 0.370), EFS2 (48.9 vs 30.3, log-rank p = 0.210) and OS (87.3 vs 46.9, log-rank p = 0.067) were not statistically significant. Conclusions: In this large multicenter study, RM after 1L BR was associated with improved EFS and OS, supporting its use in routine practice for patients with newly diagnosed MCL.