Outcomes >=1 year after transitioning from treatment with ibrutinib (IBRU) in the ASPEN study to zanubrutinib (ZANU).

Abstract

Introduction: ASPEN (NCT03053440; phase 3) compared the BTK inhibitor (BTKi) zanu with ibru in patients (pts) with MYD88-mutated Waldenstrom macroglobulinemia (WM). LTE1 (NCT04170283) is a zanu long-term extension study. We report clinical outcomes >=1 yr after transition from ibru in ASPEN to zanu in LTE1. Method(s): In LTE1, ibru-treated pts from ASPEN began 320 mg/day zanu. Disease response was assessed every 6 months by modified Owen criteria or as no evidence of progressive disease at investigator discretion. Safety/efficacy outcomes were analyzed ad hoc. Result(s): Between Jun 26, 2020 and Jun 23, 2022, 47 ibru-treated pts from ASPEN enrolled in LTE1; most (79%) had relapsed/refractory WM prior to ASPEN. At LTE1 enrollment, median age was 73 yrs; median time from ASPEN discontinuation to zanu initiation was 0.07 months. As of Jun 23, 2023, 40 pts (85%) remained on study treatment. Median treatment duration was 50.4 months for ibru prior to transition and 15.3 months for zanu. During LTE1, grade >=3/serious treatment-emergent AEs (TEAEs) occurred in 23%/13% of pts. Infections (6.4%; all COVID-19) were the only grade >=3 TEAEs in >2 pts; no serious TEAEs affected >2 pts. Most ibru TEAEs of interest for BTKis did not recur/worsen after zanu transition (except infections [n=3, all COVID-19], anemia [n=1], neutropenia [n=1]). Six of 7 pts with cardiovascular AEs (8 events) in LTE1 had >=1 ibru-emergent cardiovascular AE during ASPEN. No worsening or new hypertension occurred after zanu transition. There was no recurrence or worsening of atrial fibrillation (AF)/flutter; 1 new AF case occurred (LTE1 day 12) in a pt with extensive cardiovascular history and concurrent pericarditis (LTE1 day 10). No cardiovascular TEAE led to death in LTE1. Two deaths occurred (both due to COVID-19). Overall response at end of ASPEN was maintained or improved at BOR in LTE1 in 96% (n=44/46) of efficacy-evaluable pts. Median [IgM] change was-36 mg/dL; [IgM] was stable/decreased in 29 pts (73%) from last ASPEN response assessment to BOR in LTE1. Conclusion(s): Following zanu transition, at median ibru treatment duration of 50.4 months, most ibru-emergent TEAEs of interest for BTKis did not recur/worsen at 15-months median zanu treatment duration. Response was maintained or improved in 96% (n=44/46) of efficacy-evaluable pts. Although limited, the data suggest that transitioning ibru-tolerant pts with WM to zanu does not compromise safety or efficacy; longterm follow-up is ongoing.