Dr Visco on the Design of the FIL_V-RBAC Trial of RBAC Plus Venetoclax in High-Risk MCL

“With this study, we aimed to investigate whether the addition of venetoclax to the RBAC regimen could improve the progression-free survival of patients with high-risk MCL.”

Carlo Visco, MD, an associate professor of hematology in the Department of Medicine, coordinator of the Lymphoma Team in the Hematology and Bone Marrow Transplant Unit in the Section of Biomedical Innovation in the Department of Engineering for Innovative Medicine at the University of Verona, discussed the design and patient enrollment criteria of the phase 2 FIL_V-RBAC study (NCT03567876) of bendamustine plus rituximab (Rituxan; BR) plus intermediate-dose cytarabine (RBAC) followed by venetoclax (Venclexta) in older patients with high-risk mantle cell lymphoma (MCL).

RBAC remains a standard initial regimens for older, fit patients with MCL, as recognized in international guidelines, Visco began. The core investigative aim of the FIL_V-RBAC study was to investigate whether adding venetoclax to the existing RBAC framework could enhance the progression-free survival of patients characterized as having high-risk MCL.

The trial’s inclusion criteria required histologically confirmed, treatment-naive MCL patients at least 65 years of age who were categorized as “fit” according to the Fondazione Italiana Linfomi modified comprehensive geriatric assessment. The multicenter, single-arm study was conducted across 35 institutions within the Fondazione Italiana Linfomi.

Crucially, the study differentiated patient treatment based on risk profile, based on the importance of tailored application, Visco explained. Patients were stratified during screening into low-risk or high-risk groups based on specific clinical and genetic features. High-risk MCL was strictly defined as the presence of at least 1 of 4 features: a blastoid morphology, a Ki-67 proliferation index of 30% or higher, the presence of a TP53 gene mutation, or the presence of a 17p deletion.

Patients presenting with a low-risk profile were treated solely with 6 cycles of intravenous RBAC. The high-risk cohort, however, received only 4 cycles of RBAC, followed by consolidation therapy using fixed-duration oral venetoclax at 800 mg per day for 4 months and subsequently as maintenance therapy at 400 mg per day for 20 months. This distinction allowed researchers to combine or split the populations to see the efficacy of RBAC alone in low-risk patients vs the efficacy of RBAC plus venetoclax in high-risk patients, Visco concluded.