{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:12:36Z","timestamp":1793142756283,"version":"4.5.0"},"reference-count":18,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"6","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,2,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>BRUIN CLL-313 is a randomized, open-label, global phase III study comparing the efficacy and safety of pirtobrutinib, a highly selective, noncovalent Bruton tyrosine kinase inhibitor (BTKi), against bendamustine plus rituximab (BendaR), a common frontline chemoimmunotherapy, in treatment-na\u00efve patients with chronic lymphocytic leukemia\/small lymphocytic lymphoma (CLL\/SLL).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Patients with previously untreated CLL\/SLL without del(17p) were randomly assigned 1:1 to continuous pirtobrutinib monotherapy or BendaR, stratified by immunoglobulin heavy chain gene mutation status and Rai stage. The primary end point was independent review committee (IRC)\u2013assessed progression-free survival (PFS); secondary end points included overall survival (OS), investigator (INV)\u2013assessed PFS, safety, and tolerability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Overall, 282 patients were randomly assigned to receive pirtobrutinib (n = 141) or BendaR (n = 141). IRC-assessed PFS was significantly improved with pirtobrutinib versus BendaR (hazard ratio [HR], 0.199 [95% CI, 0.107 to 0.367];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .0001), and the 24-month PFS rate was 93.4% (95% CI, 87.6 to 96.5) and 70.7% (95% CI, 61.5 to 78.1), respectively. INV-assessed PFS similarly favored pirtobrutinib (HR, 0.186 [95% CI, 0.093 to 0.371]). Interim analysis of OS favored pirtobrutinib (median follow-up 32 months; HR, 0.257 [95% CI, 0.070 to 0.934]) despite an effective crossover rate of 52.9%. In patients receiving pirtobrutinib versus BendaR: adverse event (AE)\u2013related dose reductions occurred in 3.6% versus 31.1% of patients; grade \u22653 treatment-emergent AEs (TEAEs) occurred in 40.0% versus 67.4% of patients; and treatment discontinuations because of TEAEs occurred in 4.3% versus 15.2% of patients, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Pirtobrutinib demonstrated superiority over BendaR in IRC-assessed PFS in treatment-na\u00efve CLL\/SLL. OS trends favored pirtobrutinib despite the study design allowing for crossover. Pirtobrutinib was well tolerated, consistent with its known safety profile, and more favorable than BendaR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-02380","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T13:10:07Z","timestamp":1765285807000},"page":"466-475","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":20,"title":["BRUIN CLL-313: Randomized Phase III Trial of Pirtobrutinib Versus Bendamustine Plus Rituximab in Untreated Patients With Chronic Lymphocytic Leukemia\/Small Lymphocytic Lymphoma"],"prefix":"10.1200","volume":"44","clinical-trial-number":[{"clinical-trial-number":"nct05023980","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1879-8084","authenticated-orcid":false,"given":"Wojciech","family":"Jurczak","sequence":"first","affiliation":[{"name":"National Research Institute of Oncology, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Kwiatek","sequence":"additional","affiliation":[{"name":"AIDPORT Clinical Trials Hospital, Skorzewo, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4178-7837","authenticated-orcid":false,"given":"Jaroslaw","family":"Czyz","sequence":"additional","affiliation":[{"name":"Department of Hematology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Torun, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ederson","family":"Roberto de Mattos","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Amaral Carvalho, Jau, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0578-126X","authenticated-orcid":false,"given":"Ki-Seong","family":"Eom","sequence":"additional","affiliation":[{"name":"Catholic Hematology Hospital, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0648-4416","authenticated-orcid":false,"given":"Alexander","family":"Egle","sequence":"additional","affiliation":[{"name":"Third Medical Department for Hematology, Oncology, Hemostaseology, Infectious Disease and Rheumatology, Paracelsus University Hospital, Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4955-3039","authenticated-orcid":false,"given":"Anna","family":"Panovska","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hematology and Oncology, Masaryk University, Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4698-8600","authenticated-orcid":false,"given":"Zhanet Grudeva","family":"Popova","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Medical University of Plovdiv, Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3877-2258","authenticated-orcid":false,"given":"Hsuan-Jen","family":"Shih","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan R.O.C"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8171-0674","authenticated-orcid":false,"given":"Luis Felipe","family":"Casado Montero","sequence":"additional","affiliation":[{"name":"HM CIOCC MADRID (Centro Integral Oncol\u00f3gico Clara Campal), Instituto de Investigaci\u00f3n Sanitaria HM Hospitales, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5630-9862","authenticated-orcid":false,"given":"Paolo","family":"Sportoletti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Institute of Hematology Centro di Ricerca Emato-Oncologica (CREO), University of Perugia, Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vu Minh","family":"Hua","sequence":"additional","affiliation":[{"name":"Liverpool Hospital, Liverpool, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James T.","family":"D'Olimpio","sequence":"additional","affiliation":[{"name":"Clinical Research Alliance, Westbury, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4951-960X","authenticated-orcid":false,"given":"Shinsuke","family":"Iida","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Ito","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, 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