PATIENT REPORTED OUTCOMES FROM BRUIN CLL-321: PHASE 3 TRIAL COMPARING PIRTOBRUTINIB TO IDELALISIB/RITUXIMAB OR BENDAMUSTINE/RITUXIMAB IN COVALENT BTKi PRETREATED CLL/SLL
P. Barr, 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, J. P. Sharman
{"title":"PATIENT REPORTED OUTCOMES FROM BRUIN CLL-321: PHASE 3 TRIAL COMPARING PIRTOBRUTINIB TO IDELALISIB/RITUXIMAB OR BENDAMUSTINE/RITUXIMAB IN COVALENT BTKi PRETREATED CLL/SLL","authors":"P. Barr, 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, J. P. Sharman","doi":"10.1002/hon.70094_219","DOIUrl":null,"url":null,"abstract":"<p><b>Introduction:</b> The phase 3, randomized trial BRUIN CLL-321 assessed the safety and efficacy of pirtobrutinib compared to investigators choice (IC) of idelalisib plus rituximab (IdelaR) or bendamustine + rituximab (BR) in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) previously treated with a covalent BTK inhibitor (cBTKi). BRUIN CLL-321 showed significantly improved progression-free survival and longer time to next treatment or death with pirtobrutinib compared to IdealR/BR. Exploratory endpoints of the trial assessed changes from baseline in patient reported outcomes (PROs) through week 25 for patients treated with pirtobrutinib compared to IdelaR/BR.</p><p><b>Methods:</b> Patients with relapsed/refractory CLL/SLL, who received at least one prior cBTKi, were enrolled in BRUIN CLL-321. Endpoints included the evaluation of PROs between groups, as measured by three tools: the EORTC QLQ-C30 physical function (PF) scale, a CLL/SLL-related symptoms scale, and a fatigue scale expanded from the QLQ-C30 fatigue scale. PROs were collected every 4 weeks during study treatment. A positive least square means difference (LSM<sub>d</sub>) PF score reflected PF improvement from baseline in the pirtobrutinib group, while a negative change in symptoms or fatigue LSM<sub>d</sub> 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 a priori from Cocks et al. (<i>JCO</i> 29 (1):89–96, 2011). The statistical testing of PRO endpoints was not type-1 error controlled and thus descriptive in nature.</p><p><b>Results:</b> A total of 119 patients were randomized to each treatment arm (<i>N</i> = 238). PRO completion rate was 82.1% at baseline and remained above 80% at each subsequent assessment through Week 25. CLL/SLL-related symptoms were clinically meaningfully lower in the pirtobrutinib group versus IdelaR/BR at Week 9 (LSM<sub>d</sub>, −7.3 [standard error (SE), 2.2]), Week 13 (LSM<sub>d</sub>, −6.7 [SE, 2.3]), Week 17 (LSM<sub>d</sub>, −4.6 [SE, 2.3]), and Week 21 (LSM<sub>d</sub>, −7.0 [SE, 2.3]). Patients in the pirtobrutinib group reported lower fatigue scores versus those receiving IdelaR/BR at Week 9 (LSM<sub>d</sub>, −9.0 [SE, 2.9]), Week 13 (LSM<sub>d</sub>, −6.7 [SE, 3.0]), and Week 21 (LSM<sub>d</sub>, −6.9 [SE, 3.1]). Patients in the pirtobrutinib group also reported better PF versus IdelaR/BR at Weeks 13 (LSM<sub>d</sub>, 5.6 [SE, 2.4]) and 21 (LSM<sub>d</sub>, 5.9 [SE, 2.5]).</p><p><b>Conclusions:</b> These analyses suggest a meaningful and clinically relevant improvement in CLL/SLL-related symptoms, physical functioning, and fatigue at most assessments between baseline and Week 25 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.</p><p><b>Research</b> <b>funding declaration:</b> Sponsored by Eli Lilly and Company</p><p><b>Encore Abstract:</b> EHA 2025</p><p><b>Keyword:</b> chronic lymphocytic leukemia (CLL)</p><p><b>Potential sources of conflict of interest:</b></p><p><b>P. Barr</b></p><p><b>Consultant or advisory role:</b> Celgene, TG Therapeutics, Pharmacyclics LLC an AbbVie Company, Gilead, Bristol Myers Squibb, AstraZeneca, Merck, Janssen, MEI Pharma, MorphoSys, Seagen</p><p><b>Other remuneration:</b> Genentech, Pharmacyclics LLC, AbbVie company</p><p><b>P. Ghia</b></p><p><b>Consultant or advisory role:</b> Galapagos, Johnson&Johnson, BeiGen, AstraZeneca, AbbvVie, Loxo@Lilly, MSD, Galapagos, Roche</p><p><b>Other remuneration:</b> Bristol Myers Squibb, AbbvVie</p><p><b>D. Rossi</b></p><p><b>Consultant or advisory role:</b> AbbVie, Janssen, AstraZeneca</p><p><b>Other remuneration:</b> AstraZeneca, AbbVie, Janssen; Research Funding: AbbVie, Janssen, AstraZeneca</p><p><b>E. Ferrant</b></p><p><b>Consultant or advisory role:</b> AstraZeneca, BeiGene, Janssen, Cilag, AbbVie, Gilead: Honoraria; AstraZeneca, BeiGene, Janssen</p><p><b>F. De la Cruz Vicente</b></p><p><b>Consultant or advisory role:</b> Takeda, Roche, Kyowa Kirin, Janssen, Eusapharma, Beigene, Abbvie</p><p><b>D. Maruyama</b></p><p><b>Consultant or advisory role:</b> Pfizer,</p><p><b>Honoraria:</b> MSD, AbbVie, Janssen, Ono, AstraZeneca, SymBio, Celgene, Eisai, Bristol Myers Squibb, Sanofi, Takeda, Zenyaku Mundipharma, Nippon Shinyaku, Astellas, Kyowa Kirin Chugai</p><p><b>Other remuneration:</b> MSD, Otsuka, Janssen, Ono, Novartis, Celgene, Taiho, Eisai, Bristol Myers Squibb, Sanofi, Takeda, Chugai, Amgen, Astellas, Biopharma, Kyowa Kirin</p><p><b>V. Banerji</b></p><p><b>Honoraria:</b> Janssen, AstraZeneca, Merck, Beigene, Abbvie,</p><p><b>Other remuneration:</b> Lymphoma Canada, AstraZeneca, CancerCare Manitoba Foundation, Hairy Cell Leukemia Foundation, CIHR, Biogen, U of M, LLSC</p><p><b>S. Namburi</b></p><p><b>Consultant or advisory role:</b> Bristol-Myers Squibb/Celgene/Juno; Bristol-Myers Squibb/Celgene/Juno; Janssen; ORIC Pharmaceuticals; Regeneron; Sanofi</p><p><b>Honoraria:</b> Medscape</p><p><b>R. Greil</b></p><p><b>Honoraria:</b> Roche</p><p><b>Other remuneration:</b> Roche</p><p><b>A. Loubert</b></p><p><b>Employment or leadership position:</b> Modus Outcomes</p><p><b>K. Creel</b></p><p><b>Employment or leadership position:</b> Modus Outcomes</p><p><b>Consultant or advisory role:</b> Geron</p><p><b>L. M. Hess</b></p><p><b>Employment or leadership position:</b> Eli Lilly and Company</p><p><b>N. Payakachat</b></p><p><b>Employment or leadership position:</b> Eli Lilly and Company</p><p><b>A. S. Ruppert</b></p><p><b>Employment or leadership position:</b> Eli Lilly and Company</p><p><b>D. Wang</b></p><p><b>Employment or leadership position:</b> Eli Lilly and Company</p><p><b>P. Abada</b></p><p><b>Employment or leadership position:</b> Eli Lilly and Company</p><p><b>C. C. Leow</b></p><p><b>Employment or leadership position:</b> Eli Lilly and Company</p><p><b>M. Hill</b></p><p><b>Employment or leadership position:</b> Eli Lilly and Company</p><p><b>C. C. Coombs</b></p><p><b>Consultant or advisory role:</b> AbbVie, Octapharma, Beigene, Lilly, Genentech</p><p><b>Honoraria:</b> AbbVie, Allogene, AstraZeneca, MEI Pharma, Janssen, Mingsight, Beigene, Lilly, Genentech</p><p><b>Other remuneration:</b> Pfizer, Bluebird Bio, Geron. Genentech</p><p><b>J. P. Sharman</b></p><p><b>Consultant or advisory role:</b> AbbVie, Eli Lilly and Company, AstraZeneca, BMS, Genentech, Merck, Genmab</p><p><b>Honoraria:</b> AbbVie, Eli Lilly and Company, ADC Therapeutics, TG Therapeutics, Pharmacyclics LLC, an AbbVie Company</p><p><b>Other remuneration:</b> AbbVie, Eli Lilly and Company, BeiGene, BMS, Genentech</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_219","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematological Oncology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/hon.70094_219","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: The phase 3, randomized trial BRUIN CLL-321 assessed the safety and efficacy of pirtobrutinib compared to investigators choice (IC) of idelalisib plus rituximab (IdelaR) or bendamustine + rituximab (BR) in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) previously treated with a covalent BTK inhibitor (cBTKi). BRUIN CLL-321 showed significantly improved progression-free survival and longer time to next treatment or death with pirtobrutinib compared to IdealR/BR. Exploratory endpoints of the trial assessed changes from baseline in patient reported outcomes (PROs) through week 25 for patients treated with pirtobrutinib compared to IdelaR/BR.
Methods: Patients with relapsed/refractory CLL/SLL, who received at least one prior cBTKi, were enrolled in BRUIN CLL-321. Endpoints included the evaluation of PROs between groups, as measured by three tools: the EORTC QLQ-C30 physical function (PF) scale, a CLL/SLL-related symptoms scale, and a fatigue scale expanded from the QLQ-C30 fatigue scale. PROs were collected every 4 weeks during study treatment. 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 a priori from Cocks et al. (JCO 29 (1):89–96, 2011). The statistical testing of PRO endpoints was not type-1 error controlled and thus descriptive in nature.
Results: A total of 119 patients were randomized to each treatment arm (N = 238). PRO completion rate was 82.1% at baseline and remained above 80% at each subsequent assessment through Week 25. CLL/SLL-related symptoms were clinically meaningfully lower in the pirtobrutinib group versus IdelaR/BR at Week 9 (LSMd, −7.3 [standard error (SE), 2.2]), Week 13 (LSMd, −6.7 [SE, 2.3]), Week 17 (LSMd, −4.6 [SE, 2.3]), and Week 21 (LSMd, −7.0 [SE, 2.3]). Patients in the pirtobrutinib group reported lower fatigue scores versus those receiving IdelaR/BR at Week 9 (LSMd, −9.0 [SE, 2.9]), Week 13 (LSMd, −6.7 [SE, 3.0]), and Week 21 (LSMd, −6.9 [SE, 3.1]). Patients in the pirtobrutinib group also reported better PF versus IdelaR/BR at Weeks 13 (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 Week 25 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.
Researchfunding declaration: Sponsored by Eli Lilly and Company
Encore Abstract: EHA 2025
Keyword: chronic lymphocytic leukemia (CLL)
Potential sources of conflict of interest:
P. Barr
Consultant or advisory role: Celgene, TG Therapeutics, Pharmacyclics LLC an AbbVie Company, Gilead, Bristol Myers Squibb, AstraZeneca, Merck, Janssen, MEI Pharma, MorphoSys, Seagen
Other remuneration: Genentech, Pharmacyclics LLC, AbbVie company
期刊介绍：
Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged:
-Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders
-Diagnostic investigations, including imaging and laboratory assays
-Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases
-Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies
-Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems.
Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
