{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:36:57Z","timestamp":1792525017554,"version":"4.5.0"},"reference-count":20,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"22","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Pirtobrutinib, a noncovalent, Bruton tyrosine kinase inhibitor (BTKi), has shown clinical efficacy and a favorable safety profile. BRUIN CLL-321 was an open-label, randomized phase III study conducted exclusively in patients with R\/R chronic lymphocytic leukemia (CLL)\/small lymphocytic lymphoma (SLL) previously treated with cBTKi, and compared pirtobrutinib with investigator's choice (IC) of idelalisib\/rituximab (IdelaR) or bendamustine\/rituximab (BR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Patients were randomly assigned 1:1 to receive pirtobrutinib (200 mg once daily) or IC of IdelaR or BR, and were stratified by previous use of venetoclax and del(17p). The primary end point was independent review committee\u2013assessed progression-free survival (PFS). Secondary end points included time to next treatment or death (TTNT), overall survival (OS), and safety. The primary PFS end point was met at the time of the primary analysis (August 29, 2023), and updated results are reported from the final OS analysis (August 29, 2024).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      A total of 238 patients were randomly assigned to receive pirtobrutinib (n = 119) or IC (n = 119; IdelaR [n = 82], BR [n = 37]). The PFS hazard ratio (HR) was 0.54 ([95% CI, 0.39 to 0.75];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .0002), with a median PFS of 14 months (95% CI, 11.2 to 16.6) in the pirtobrutinib group and 8.7 months (95% CI, 8.1 to 10.4) with IC. The unadjusted OS HR was 1.09 ([95% CI, 0.68 to 1.75];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .7202), and 18-month OS rate was 73.4% (95% CI, 63.9 to 80.7) in the pirtobrutinib group and 70.8% (95% CI, 60.9 to 78.7) with IC. Median TTNT was 24 months (95% CI, 17.8 to 29.7) with pirtobrutinib versus 10.9 months (95% CI, 8.7 to 12.5) with IC (HR, 0.37 [95% CI, 0.25 to 0.52]). At a median follow-up of 17.2 months, grade \u22653 treatment-emergent adverse events (AEs) were lower with pirtobrutinib (57.7%) than IC (73.4%). Treatment discontinuation due to AE occurred in 20 (17.2%) patients receiving pirtobrutinib and 38 (34.9%) patients receiving IC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Pirtobrutinib improved PFS and TTNT, and demonstrated favorable tolerability, versus IdelaR\/BR in exclusively cBTKi pretreated patients with CLL\/SLL.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-00166","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T15:59:18Z","timestamp":1749225558000},"page":"2538-2549","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":50,"title":["Phase III Trial of Pirtobrutinib Versus Idelalisib\/Rituximab or Bendamustine\/Rituximab in Covalent Bruton Tyrosine Kinase Inhibitor\u2013Pretreated Chronic Lymphocytic Leukemia\/Small Lymphocytic Lymphoma (BRUIN CLL-321)"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct04666038","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5611-6115","authenticated-orcid":true,"given":"Jeff P.","family":"Sharman","sequence":"first","affiliation":[{"name":"Willamette Valley Cancer Institute and Research Center, US Oncology Research, Eugene, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2901-0769","authenticated-orcid":true,"given":"Talha","family":"Munir","sequence":"additional","affiliation":[{"name":"Department of Haematology, St James's University Hospital, Leeds, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Grosicki","sequence":"additional","affiliation":[{"name":"Department of Cancer Prevention, Medical University of Silesia, Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey E.","family":"Roeker","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center NY, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5144-6710","authenticated-orcid":true,"given":"John M.","family":"Burke","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute and Rocky Mountain Cancer Centers, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine I.","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology &amp; 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