BR induction + BCL2 inhibitor venetoclax/CD20 rituximab consolidation delivers 83% BM uMRD and 87.5% 3-year PFS in frontline CLL

Short-course bendamustine/rituximab (alkylator + anti-CD20) followed by venetoclax/rituximab (BCL2 inhibitor + anti-CD20) was tested as a time-limited, single-arm Phase 2 regimen in previously untreated CLL/SLL requiring therapy (NCT03609593; n=42; median age 61.5; 64% unmutated IGHV; 29% complex karyotype; 10% TP53 aberrancy), using 3 cycles of BR then venetoclax ramp to 400mg daily with 6 cycles of rituximab and venetoclax continued to 12 total cycles (15 months total therapy). End-of-treatment ORR was 86% ITT (CR/CRi 64%) and 100% in efficacy-evaluable patients (CR/CRi 75%), with uMRD 83% in bone marrow and 84% in blood (evaluable); 3-year PFS and OS were 87.5% and 92.7%. Safety signals were largely hematologic (febrile neutropenia 12%); BR “downstaged” TLS risk and no TLS events occurred—while today’s frontline SOC is typically chemo-free fixed-duration venetoclax/obinutuzumab (CLL14) or continuous BTK-inhibitor–based therapy, this study’s ~88% 3-year PFS looks directionally similar to the ~high-80% 3-year PFS benchmark reported for ibrutinib/rituximab in younger frontline patients (E1912), albeit with cross-trial and population differences.