Impact of covalent BTK inhibitor dose modifications on outcomes in CLL/SLL: retrospective real-world study

Covalent BTK inhibitors (cBTKis) are the cornerstone of chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) therapy. A 7-year retrospective study at Shanghai Jiao Tong University School of Medicine (China) investigated the impact of cBTKi dose modifications in a real-world CLL/SLL cohort. The study included 324 patients with a median follow-up of 42 months. Dose modifications were classified as dose interruption (DI) or dose reduction (DR). Primary endpoint were prorgression-free survival (PFS) and overall survival (OS). The 42-month PFS rate was 70.2%. Of 324 patients, 229 (70.7%) experienced DR or DI; infections were the predominant cause (61.9%). The full-dose group (n=90) demonstrated superior 4-year PFS-rate (93% versus 58%; p<0.001) and 4-year OS rate (98% versus 76%; p=0.007). Early modifications (0-3 months) were independent predictors of inferior PFS (HR 3.93; p=0.008) and OS (HR 3.29; p=0.014). Prolonged DI 9.14 days) was associated with inferior PFS (HR 2.64) and OS (HR 2.15), whereas DR and short DI (≤ 14 days) had neglibible impact. Early (0-3 months) prolonged DI was devastating (3-year PFS rate 41.2%; HR 3.84; p<0.001). cBTKi switching (n=82; 100% nonprogression-driven) shortenened DI (median 6 versus 14 days) and was independently associated with superior OS (HR 0.34; p=0.018) and PFS (HR 0.36; p=0.022). The authors conclude that early prolonged DI is a dominant adverse prognostic factor in cBTKi-treated CLL/SLL. Proactive switching minimizes treatment gaps and improves survival.xtagstartz/p>