Rituximab, Bendamustine and Cytarabine Followed By Venetoclax (V-RBAC) in High-Risk Elderly Patients with Mantle Cell Lymphoma

The R-BAC regimen is considered among standard first-line treatment for elderly fit patients with mantle cell lymphoma (MCL). In the previous R-BAC500 FIL trial, patients with the blastoid variant and/or high Ki67 proliferative index (High Risk - HR-) had a significantly higher risk of progression (2-years PFS of 40%), as compared to classical histologies and low proliferative index (Low Risk -LR-). When treated with R-BAC, LR patients had excellent outcome (median PFS not reached after 7 years), although no maintenance therapy was delivered. For this reason we designed a phase 2 trial that enrolled patients from 35 centers of the Fondazione Italiana Linfomi (FIL). At study entry, patients were centrally reviewed and stratified as “low risk (LR)”, or “high risk (HR)”, depending on morphology (blastoid versus others), Ki67 expression (≥30% versus others), TP53 mutation/TP53 deletions (present versus not). Patients with any of the three risk factors were classified as HR. The primary endpoint was 2-years progression-free survival (PFS) for the HR patients. Patients had to be aged ≥65 years and fit according to the geriatric CGA assessment, or age ≤64 years if not eliglible to high-dose chemotherapy plus transplantation. Asymptomatic patients with non-nodal disease were excluded. Treatment consisted of 6 cycles of R-BAC (rituximab 375 mg/m2 d 1; bendamustine 70 mg/m2 d 1,2; cytarabine 500 mg/m2 d 1,2,3) for LR patients. HR patients received abbreviated induction with a maximum of 4 R-BAC followed by consolidation (4 months, 800 mg/d), and maintenance (20 months, 400 mg/d) with venetoclax. First patient was included on the 3rd of september, 2018, and last patient on the 20th of july, 2021. Overall, 140 patients were enrolled, of whom 52 were HR (37%). Median age was 72 (range 57-79), and 75% were males. The prevalence of TP53 mutations and deletions in the whole series was 21%, and 13%, respectively; Ki67 was ≥30% in 24%, and the blastoid variant was diagnosed in 9%. Demographic characteristics of HR versus LR patients (127 patients with available data at the present time) are reported in Table 1A. Median follow-up was 9 months (range 0-34). The two groups (HR and LR) had similar age, gender, and MIPI, but differed for LDH, and SUVmax at diagnosis, both being significantly more elevated in the HR group. The VR-BAC trial represents the first prospective study that stratified patients with MCL to different frontline treatments according to centralized on-time ev