Pirtobrutinib Versus Ibrutinib in Treatment-Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

作者：Jennifer A. Woyach, Lugui Qiu, Sebastian Grosicki, Tomasz Wróbel, Marcelo Capra, Jarosław Czyż, Shuhua Yi, Ki‐Seong Eom, Anna Panovská, Wojciech Jurczak, Kamel Laribi, Lutz Jacobasch, Ross Baker, Richy Agajanian, Alejandro Berkovits, Muhıt Özcan, Stéphane Leprêtre, Catherine C. Coombs, Paula Cramer, Katharine L. Lewis, Marisa Hill, Katherine Bao, Yuanyuan Bian, Sílvia Ribeiro, Naleen Raj Bhandari, Amy S. Ruppert, Ching Ching Leow, William G. Wierda · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco-25-02477 · 被引用次数：20 · 研究领域：Chronic Lymphocytic Leukemia Research、Lymphoma Diagnosis and Treatment、Chronic Myeloid Leukemia Treatments

PURPOSE 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. PATIENTS AND METHODS 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 with R / R disease. RESULTS The study met its primary end points, demonstrating statistically significant noninferiority (NI) of IRC-ORR for pirtobrutinib versus ibrutinib in both the ITT (87.0% [95% CI, 82.9 to 90.4] v 78.5% [95% CI, 73.7 to 82.9]; ORR ratio = 1.11 [95% CI, 1.03 to 1.19]; two-sided P < .0001) and R/R populations (n = 437; 84.0% [95% CI, 78.5 to 88.6] v 74.8% [95% CI, 68.5 to 80.4]; ORR ratio = 1.12 [95% CI, 1.02 to 1.24]; two-sided P < .0001). In TN patients (n = 225), IRC-ORR was 92.9% (95% CI, 86.4 to 96.9) with pirtobrutinib versus 85.8% (95% CI, 78.0 to 91.7) with ibrutinib. Investigator assessed ORR results were consistent. Investigator-assessed progression-free survival (PFS) fa...