biostudies-literatureUnknownWoyach JA<h4>Purpose</h4>Pirtobrutinib, a highly selective, noncovalent Bruton tyrosine kinase inhibitor (BTKi), has shown efficacy and safety in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who received prior covalent BTKi. We report results, to our knowledge, from the first randomized head-to-head comparison of pirtobrutinib versus ibrutinib in BTKi-naïve CLL/SLL in both treatment-naïve (TN) patients and patients with relapsed/refractory (R/R) disease.<h4>Patients and methods</h4>Patients (N = 662) were randomly assigned 1:1 to receive pirtobrutinib or ibrutinib. All patients were BTKi-naïve. Primary end points were overall response rate (ORR) by independent review committee (IRC) among all randomly assigned patients (intention to treat [ITT]) and in patients wiJournal of clinical oncology : official journal of the American Society of Clinical OncologyJCO2502477https://www.ebi.ac.uk/biostudies/studies/S-EPMC12904240biostudies-literaturePirtobrutinib Versus Ibrutinib in Treatment-Naive and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.PMC12904240Agajanian RYi SEom KSWoyach JAOzcan MQiu LBerkovits ABao KBian YHill MBhandari NRLeow CCCoombs CCPanovska AWrobel TLewis KLDe Batista Ribeiro SRGrosicki SCzyz JCapra MLaribi KRuppert ASCramer PJurczak WJacobasch LLepretre SWierda WGBaker RfalsePirtobrutinib Versus Ibrutinib in Treatment-Naive and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.<h4>Purpose</h4>Pirtobrutinib, a highly selective, noncovalent Bruton tyrosine kinase inhibitor (BTKi), has shown efficacy and safety in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who received prior covalent BTKi. We report results, to our knowledge, from the first randomized head-to-head comparison of pirtobrutinib versus ibrutinib in BTKi-naïve CLL/SLL in both treatment-naïve (TN) patients and patients with relapsed/refractory (R/R) disease.<h4>Patients and methods</h4>Patients (N = 662) were randomly assigned 1:1 to receive pirtobrutinib or ibrutinib. All patients were BTKi-naïve. Primary end points were overall response rate (ORR) by independent review committee (IRC) among all randomly assigned patients (intention to treat [ITT]) and in patients wi2025-01-01T00:00:00Z2025 Dec2026-07-15T22:02:26.777Z2026-07-09T13:09:31.896ZS-EPMC129042404135378710.1200/JCO-25-02477