Patient Reported Outcomes in BRUIN CLL-321: A Phase 3 Trial of Pirtobrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in BTK Inhibitor Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Author(s)
Paul M. Barr, MD1, Davide Rossi, MD2, Emmanuelle Ferrant, MD3, Fátima de la Cruz, MD4, Dai Maruyama, MD5, Versha Banerji, MD6, Patrick Cobb, MD7, Swathi Namburi, MD8, Richard Greil, MD9, Jeff P. Sharman, MD10, Angely Loubert, PhD, PharmD11, Kristin Creel, MSc11, Lisa M. Hess, PhD12, Nalin Payakachat, BSc, MSc, PhD12, Amy S Ruppert, PhD12, Denise Wang, PhD12, Paolo B. Abada, MD12, Ching Ching Leow, PhD12, Marisa Hill, MD, MS12, Catherine C. Coombs, MD13, Paolo Ghia, MD, PhD14.
1Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 2Istiuto Oncologico della Svizzera Italiana, Bellinzona, Switzerland, 3Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d’Hématologie Clinique, Pierre-Bénite, France, 4Hospital Universitario Virgen del Rocío, Sevilla, Spain, 5The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan, 6CancerCare Manitoba, Winnipeg, MB, Canada, 7St Vincent Frontier Cancer Center, Miles City, MT, USA, 8Swedish Cancer Institute, Seattle, WA, USA, 9Paracelsus Medical University, Salzberg, Austria, 10Willamette Valley Cancer Institute and Research Center, US Oncology Research, Eugene, OR, USA, 11Modus Outcomes, Lyon, France, 12Eli Lilly and Company, Indianapolis, IN, USA, 13University of California Irvine, Irvine, CA, USA, 14Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milano, Italy.
1Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 2Istiuto Oncologico della Svizzera Italiana, Bellinzona, Switzerland, 3Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d’Hématologie Clinique, Pierre-Bénite, France, 4Hospital Universitario Virgen del Rocío, Sevilla, Spain, 5The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan, 6CancerCare Manitoba, Winnipeg, MB, Canada, 7St Vincent Frontier Cancer Center, Miles City, MT, USA, 8Swedish Cancer Institute, Seattle, WA, USA, 9Paracelsus Medical University, Salzberg, Austria, 10Willamette Valley Cancer Institute and Research Center, US Oncology Research, Eugene, OR, USA, 11Modus Outcomes, Lyon, France, 12Eli Lilly and Company, Indianapolis, IN, USA, 13University of California Irvine, Irvine, CA, USA, 14Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milano, Italy.
Presentation Documents
OBJECTIVES: BRUIN CLL-321 is the first randomized phase III clinical trial assessing the safety and efficacy of treatment entirely in patients who have been previously treated with cBTKi. BRUIN CLL-321 showed superior progression-free survival and time to next treatment or death with pirtobrutinib compared to control arm.
METHODS: Exploratory endpoints assessing within-group changes in patient reported outcomes (PROs) in patients treated with pirtobrutinib or investigators choice of idelalisib with rituximab or bendamustine with rituximab through Week 25 are reported. Patients with relapsed/refractory CLL/SLL who received at least one prior covalent BTK inhibitor (cBTKi) enrolled in BRUIN-CLL-321. Prespecified endpoints included the evaluation of PROs within-groups as measured by the EORTC QLQ-C30 physical function (PF) scale, a CLL/SLL-related Symptoms scale, and an expanded Fatigue scale. Longitudinal analyses used mixed model for repeated measures adjusted for baseline PRO scores. Estimated change from baseline in scores were interpreted following within-group change thresholds, where positive change reflects improved PF and worsened symptoms and fatigue. The statistical testing of PRO endpoints was not type-1 error controlled and the PRO analyses were exploratory.
RESULTS: A total of 119 patients were enrolled to each treatment arm (N=238). PRO completion rate was 82.1% at baseline. Within arm, pirtobrutinib demonstrated meaningful and significant (p<0.05) improvements from baseline in PF, CLL/SLL-related symptoms, and fatigue at all post-baseline assessments (least squares [LS] means change ranged from +5.4 to +8.9, -7.0 to -11.8, and -7.0 to -12.7, respectively). The control arm demonstrated numeric improvements at some, but not all assessments (LS means change ranged from +0.8 to +4.2, -0.3 to -5.0, and -0.3 to -5.8, respectively).
CONCLUSIONS: Exploratory analyses suggested meaningful improvements in CLL/SLL-related symptoms, physical functioning, and fatigue more frequently in the pirtobrutinib arm compared to control.
METHODS: Exploratory endpoints assessing within-group changes in patient reported outcomes (PROs) in patients treated with pirtobrutinib or investigators choice of idelalisib with rituximab or bendamustine with rituximab through Week 25 are reported. Patients with relapsed/refractory CLL/SLL who received at least one prior covalent BTK inhibitor (cBTKi) enrolled in BRUIN-CLL-321. Prespecified endpoints included the evaluation of PROs within-groups as measured by the EORTC QLQ-C30 physical function (PF) scale, a CLL/SLL-related Symptoms scale, and an expanded Fatigue scale. Longitudinal analyses used mixed model for repeated measures adjusted for baseline PRO scores. Estimated change from baseline in scores were interpreted following within-group change thresholds, where positive change reflects improved PF and worsened symptoms and fatigue. The statistical testing of PRO endpoints was not type-1 error controlled and the PRO analyses were exploratory.
RESULTS: A total of 119 patients were enrolled to each treatment arm (N=238). PRO completion rate was 82.1% at baseline. Within arm, pirtobrutinib demonstrated meaningful and significant (p<0.05) improvements from baseline in PF, CLL/SLL-related symptoms, and fatigue at all post-baseline assessments (least squares [LS] means change ranged from +5.4 to +8.9, -7.0 to -11.8, and -7.0 to -12.7, respectively). The control arm demonstrated numeric improvements at some, but not all assessments (LS means change ranged from +0.8 to +4.2, -0.3 to -5.0, and -0.3 to -5.8, respectively).
CONCLUSIONS: Exploratory analyses suggested meaningful improvements in CLL/SLL-related symptoms, physical functioning, and fatigue more frequently in the pirtobrutinib arm compared to control.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
PCR91
Topic
Patient-Centered Research
Topic Subcategory
Patient-reported Outcomes & Quality of Life Outcomes
Disease
SDC: Oncology