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
Year: 2025
Type: article
Abstract: 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
Authors: P. Ghia, D. Rossi, E. Ferrant, F. De La Cruz Vicente, D. Maruyama, V. Banerji, P. Cobb, S. Namburi, R. Greil, A. Loubert, K. Creel, L.M. Hess, N. Payakachat, A.S. Ruppert, D. Wang, P. Abada, C.C. Leow, M. Hill, C.C. Coombs, P. Barr, J.P. Sharman
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093123643
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