C059 | PATIENT REPORTED OUTCOMES FROM BRUIN CLL-321: A RANDOMIZED PHASE 3 TRIAL COMPARING PIRTOBRUTINIB TO IDELALISIB/RITUXIMAB OR BENDAMUSTINE/RITUXIMAB IN COVALENT BTKI PRETREATED CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA

Background: The phase 3, randomized trial BRUIN CLL-321 assessed the safety and efficacy of pirtobrutinib vs investigators choice (IC) of idelalisib+rituximab (IdelaR) or bendamustine+rituximab (BR) in patients (pts) with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) pre-treated with a covalent BTK inhibitor (cBTKi). BRUIN CLL-321 showed significantly improved progression-free survival and longer time to next treatment (tx) or death with pirtobrutinib vs IdealR/BR. Aims: Exploratory endpoints of the trial assessed changes from baseline in pt reported outcomes (PROs) through week (W) 25 for pts treated with pirtobrutinib vs IdelaR/BR. Methods: Pts with relapsed/refractory CLL/SLL, who received >1 prior cBTKi, were enrolled. Endpoints included the evaluation of PROs between groups. PROs were collected every 4W during study tx. A positive least square means difference (LSMd) PF score reflected PF improvement from baseline in the pirtobrutinib group, while a negative change in symptoms or fatigue LSMd reflected improvement in the pirtobrutinib group from baseline compared to IdelaR/BR. Longitudinal analyses used mixed model for repeated measures adjusted for baseline PRO scores. Thresholds for clinically meaningful between-group differences were defined. Results: A total of 119 pts were randomized to each tx arm (N=238). PRO completion rate was 75.2% at baseline. CLL/SLL-related symptoms were clinically meaningfully lower in the pirtobrutinib group vs IdelaR/BR at W9 (LSMd,-7.3 [standard error (SE), 2.2]), W13 (LSMd,-6.7 [SE, 2.3]), W17 (LSMd,-4.6 [SE, 2.3]), and W21 (LSMd,-7.0 [SE, 2.3]). Pts in the pirtobrutinib group reported lower fatigue scores vs those receiving IdelaR/BR at W9 (LSMd,-9.0 [SE, 2.9]), W13 (LSMd,-6.7 [SE, 3.0]), and W21 (LSMd,-6.9 [SE, 3.1]). Pts in the pirtobrutinib group also reported better PF vs IdelaR/BR at W13 (LSMd,5.6 [SE, 2.4]) and 21 (LSMd,5.9 [SE, 2.5]). Conclusions: These analyses suggest a meaningful and clinically relevant improvement in CLL/SLL-related symptoms, physical functioning, and fatigue at most assessments between baseline and W25 in the pirtobrutinib group compared to IdelaR/BR. Most PRO assessments met clinically meaningful thresholds, and for those that did not there remained a consistent directional difference in favor of pirtobrutinib, suggesting a consistent benefit in terms of PF, CLL/SLL-related symptoms, and fatigue versus IdealR/BR. Disclosure: An earlier version of these data were previously presented at EHA 2025