846TiP - Fixed-duration orelabrutinib plus bendamustine and rituximab versus continuous Bruton Tyrosine Kinase inhibitor (BTKi) in treatment-naïve chronic/small lymphocytic leukemia (CLL/SLL): A multicenter, nonrandomized, pragmatic clinical trial

Background

Survival benefits from clinical trials have established continuous BTKi as standard of care (SOC) in CLL/SLL; however, median duration of continuous BTKi in a real-world setting is short (ibrutinib: 16.5 months in FIRE study), undermining its survival benefits. BTKi plus chemoimmunotherapy or BCL-2 inhibitor, as new time-limited combination, has shown high response rates and good long-term prognosis in CLL, but whether fixed-duration (FD) regimen surpasses continuous BTKi is unclear, especially in a real-world setting. To provide more effective treatment option and clinical guidance, we perform a prospective, phase II trial with wider inclusion criteria and closer representation for real-world clinical practice, comparing FD orelabrutinib (O) plus widely used bendamustine (B) and rituximab (R) in China (called OBR) with continuous BTKi in treatment-naïve CLL/SLL. We also explore the duration of undetectable minimal residual disease (uMRD), rate of MRD negativity, and their correlation with efficacy of FD OBR.

Trial design

Adult CLL/SLL patients requiring initial therapy per iwCLL 2018 criteria and ECOG performance status of 0-2 are eligible. Patients will be enrolled from 6 centers in China and receive either FD OBR (treatment group, n=40) or SOC (continuous BTKi until outgroup; control group, n=20) in a 28-day cycle. B (70 mg/m² on days 1-2 each cycle) and R (375 mg/m² on day 1 of cycle 1 and then 500 mg/m² of cycles 2-4) are dosing for up to 4 cycles. O (150 mg daily) is given from cycle 2 to cycle 18, followed by treatment extension (maximum duration of 23 cycles throughout the study) or treatment-free observation per clinical judgment and patient preference. Study spans from May 2024 to May 2027. Primary endpoint is to compare the percentage of patients who initiated a next treatment at 30 months or die between two groups; secondary endpoints include between-group comparisons for progression-free survival, time to treatment failure, objective response rate, complete response rate, and safety; and 15-month patient compliance in control group.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.