BRUIN CLL-313: Randomized Phase III Trial of Pirtobrutinib Versus Bendamustine Plus Rituximab in Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Menés respectivement sur 662 et 282 patients atteints d'un lymphome à petits lymphocytes ou d'une leucémie lymphoïde chronique réfractaire ou récidivante, ces deux essais randomisés comparent l'efficacité, du point de vue du taux de réponse globale et de la survie sans progression, et la toxicité, d'une part du pirtobrutinib et de l'ibrutinib en traitement de première ligne, et d'autre part du pirtobrutinib et d'un traitement combinant bendamustine et rituximab
Purpose: 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-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Methods: 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)–assessed progression-free survival (PFS); secondary end points included overall survival (OS), investigator (INV)–assessed PFS, safety, and tolerability.
Results: 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]; P < .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)–related dose reductions occurred in 3.6% versus 31.1% of patients; grade ≥3 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.
Conclusion: Pirtobrutinib demonstrated superiority over BendaR in IRC-assessed PFS in treatment-naïve 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.
Journal of Clinical Oncology , résumé, 2025