FIL_V-RBAC trial: RBAC + venetoclax in older patients with high-risk MCL

The phase II FIL_V-RBAC trial (NCT03567876) investigated the addition of fixed-duration venetoclax to rituximab + bendamustine + intermediate-dose cytarabine (RBAC) in treatment-naïve patients aged ≥65 years with high-risk mantle cell lymphoma (MCL). Patients were stratified into low-risk (n = 86) or high-risk (n = 54) groups based on the presence of blastoid morphology, Ki67 ≥30%, TP53 mutations, or 17p deletion. Patients in the low-risk group received RBAC every 4 weeks for 6 cycles. Patients in the high-risk group received RBAC followed by fixed-duration venetoclax consolidation and maintenance. The primary endpoint was progression-free survival (PFS). Results were published in Lancet Haematol by Visco et al. 

Key data: The primary endpoint was met; 2-year PFS in the high-risk group was 60%, with a median PFS of 37 months. The most frequent Grade ≥3 adverse events (AEs) during venetoclax consolidation were neutropenia (28%), thrombocytopenia (7%), and skin reactions (7%). During venetoclax maintenance, the most common Grade ≥3 AEs were neutropenia (19%), thrombocytopenia (5%), and anemia (5%). One treatment-related death occurred due to tumor lysis syndrome during induction.

Key learning: This trial demonstrates that risk-stratified treatment with the addition of fixed-duration venetoclax to RBAC improves outcomes in older patients with high-risk MCL. The approach highlights the importance of identifying high-risk features at diagnosis to enable timely, risk-adapted treatment selection. Venetoclax consolidation and maintenance appears to be a feasible and effective strategy for this challenging patient population.