ABSTRACT We hypothesized that a time‐limited frontline treatment strategy with abbreviated chemoimmunotherapy followed by targeted consolidation could achieve durable disease control with manageable toxicity in CLL. We evaluated the safety and efficacy of short‐course bendamustine/rituximab (BR) induction followed by venetoclax/rituximab (VR) consolidation. In a multicenter, single‐arm Phase 2 trial (NCT03609593), previously untreated CLL/SLL needing therapy received BR for three 28‐day cycles followed by venetoclax ramp‐up to 400 mg daily plus rituximab every 28 days for six cycles; venetoclax continued to 12 cycles (total treatment, 15 months). The primary endpoint was overall response rate (ORR); key secondary endpoints included uMRD, PFS/OS, and safety per CTCAE v4. Forty‐two patients were enrolled (median age 61.5 years; 64% unmutated IGHV; 29% complex karyotype; 10% TP53 aberrancy); 93% completed all planned therapy. At end of treatment, ITT ORR was 86% (CR/CRi 64%, PR 21%); among efficacy‐evaluable patients, ORR was 100% (CR/CRi 75%). End‐of‐therapy uMRD was achieved by 83% in bone marrow and 84% in blood among efficacy‐evaluable patients. Three‐year PFS and OS were 87.5% and 92.7%. TLS risk was downstaged after BR, and no TLS events occurred. Febrile neutropenia occurred in 12% of patients. Two on‐study deaths due to COVID‐19 occurred; no Richter transformation occurred. Time‐limited BR‐VR achieved high uMRD rates and durable remissions with a manageable safety profile. While the treatment landscape in CLL has largely shifted toward chemotherapy‐free regimens, these data demonstrate the biological proof‐of‐concept that limited induction chemotherapy can effectively mitigate TLS risk and facilitate safe outpatient ramp‐up of venetoclax.
Lipsky et al. (Thu,) studied this question.
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