Long term follow-up of Rituximab plus Bendamustine and Cytarabine (R-BAC) in elderly patients with newly diagnosed MCL.

The combination of rituximab, bendamustine, and low dose cytarabine (R-BAC) has been studied in a phase 2 prospective multicenter study from the Fondazione Italiana Linfomi (FIL RBAC500). In 57 previously untreated elderly patients with mantle cell lymphoma (MCL), R-BAC was associated with complete remission rate of 91%, and 2-years progression free survival (PFS) of 81% (95%CI 68-89). Here, we report the long-term survival outcome, late toxicities, and results of minimal residual disease (MRD) evaluation. After a median follow-up of 86 months (57-107), the median overall survival (OS) and progression-free survival (PFS) were not reached. The 7-years PFS and OS rates were 55% (95%CI 41-67), and 63% (95%CI 49-74), respectively. Responding patients (n=53) had a 7-years PFS of 59% (95%CI 44-71), with no relapse or progression registered after the 6th year. At multivariate analysis blastoid/pleomorphic morphology was the strongest adverse predictive factor for PFS (p=0.04). Patients with an end of treatment negative minimal residual disease (MRD) had better, but not significant, outcomes for both PFS and OS than MRD positive patients (p=0,148 and p=0,162, respectively). There was no signal of late toxicity or increase of secondary malignancies during the prolonged follow-up. In conclusion, R-BAC, which was not followed by maintenance therapy, showed sustained efficacy over time in elderly patients with MCL. Survival outcomes compare favorably with other immuno-chemotherapy regimens (with or without maintenance), including combinations of BTK-inhibitors upfront.