Assure- interim results: a phase 3b safety study of acalabrutinib (a) in patients with chronic lymphocytic leukemia (CLL).

Abstract

Introduction: Here, we report interim results from ASSURE, a global, phase 3b safety study evaluating A monotherapy in pts with CLL in real-world clinical practice. Method(s): Pts >=18y with CLL and ECOG-PS <=2 were divided into 3 cohorts (TN, R/R, ibrutinib intolerant [IbrI]). Pts receive A 100mg twice daily for 48 cycles or until progression, toxicity, withdrawal of consent, loss to follow-up, death, or study termination. The primary objective is the frequency of treatment-emergent adverse events (TEAEs). Result(s): 552 pts had received treatment and were analyzed. Median age was 69.5y; 20% had del(17p)/TP53m and 68% uIGHV. Median number of prior lines of therapy was 1 in the R/R and 2 in the IbrI cohort. At data cutoff, 64% of pts remained on treatment; reasons for discontinuation are in the Table. Median duration of exposure was 32.1 (TN), 32.3 (R/R), and 20.5 (IbrI) months (mo). The estimated proportion of pts remaining on treatment at 30mo was 71% (TN), 62% (R/R), and 45% (IbrI). The most common TEAEs are shown in the Table. Serious TEAEs were reported in 42% of pts (TN, 38%; R/R, 50%; IbrI, 25%), including COVID-19 (COV19) (12%), pneumonia (6%), and COV19 pneumonia (5%). TEAEs led to treatment discontinuation in 19% of pts, including COV19 (n=22), COV19 pneumonia (n=9), hepatitis B reactivation (n=5), myalgia (n=3), and pneumonia (n=3). Events of clinical interest are in the Table. Deaths were reported in 65 pts (TN, 7%; R/R, 19%; IbrI, 8%) including TEAE-related deaths (n=56). Most TEAE-related deaths were in pts with COV19 (n=41). Other TEAE-related deaths in pts without COV19 (n=15) included infections/infestations (n=4) and neoplasms (n=4). No new safety risks were identified based on TEAEs or laboratory data. Conclusion(s): In this ASSURE interim analysis, the safety profile of A in pts with CLL (TN, R/R, IbrI) in a real-world setting was consistent with former studies. COV19 TEAEs, including fatal ones, occurred as study enrollment spanned the COV19 pandemic (Niemann CU, et al. Hemasphere. 2022;6(10):e780); rates of cardiac events were low, rates of infection high but manageable with low mortality excluding COV19 deaths; no new safety signals were reported.