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Jeremy S. Abramson, MD, MMSc
Jeremy S. Abramson, MD, MMSc
Posted: Thursday, January 23, 2025
Pirtobrutinib vs the investigator’s choice of therapy demonstrated superior progression-free survival in patients with covalent Bruton’s tyrosine kinase (BTK) inhibitor–treated relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), based on an updated analysis of the phase III BRUIN CLL-321 trial. At the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 886), Jeff P. Sharman, MD, of Willamette Valley Cancer Institute and Research Center, Eugene, Oregon, and colleagues also reported a more favorable safety profile for the investigational noncovalent BTK inhibitor.
Patients were randomly assigned in a 1:1 ratio to receive pirtobrutinib (n = 119) or the investigator’s choice of rituximab plus either the PI3K inhibitor idelalisib (n = 82) or the alkylating agent bendamustine (n = 37). The primary endpoint of independent review committee (IRC)-assessed progression-free survival was met at primary analysis (median follow-up = 6.1 months). With a median follow-up of 11.6 months, this updated analysis showed IRC-assessed and investigator-assessed progression-free survival hazard ratios (HRs) of 0.55 (P = .0007) and 0.42 (P < .0001), respectively. The observed IRC-assessed progression-free survival benefit with pirtobrutinib was found to be consistent across subgroups, including those with prior venetoclax treatment (HR = 0.54), complex karyotype (HR = 0.34), and TP53 mutation and/or del(17p; HR = 0.52).
Event-free survival (HR = 0.35) and the time to next treatment (HR = 0.38) were reported to be superior with pirtobrutinib. Overall survival data remain immature; the median was not reached in either arm.
The most common treatment-emergent adverse events with pirtobrutinib were anemia (20.7%), pneumonia (19.8%), neutropenia (16.4%), and diarrhea (15.5%). With the investigator’s choice of therapy, these toxicities were diarrhea (29.4%), pyrexia (25.7%), nausea (20.2%), COVID-19 (18.3%), fatigue (18.3%), decreased neutrophil count (17.4%), and increased alanine aminotransferase levels (17.4%). Fewer patients treated with pirtobrutinib experienced a treatment-emergent adverse event of grade 3 or higher (55.2% vs 71.6%).
Disclosure: For full disclosures of the study authors, visit ash.confex.com.
2024 ASH Annual Meeting & Exposition
