In a phase III trial (BRUIN CLL-321) reported in the Journal of Clinical Oncology, Sharman et al compared treatment outcomes with the noncovalent Bruton's tyrosine kinase (BTK) inhibitor pirtobrutinib vs investigator choice of idelalisib/rituximab (IdelaR) or bendamustine/rituximab (BR) in patients with relapsed or refractory, covalent BTK inhibitor–pretreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Study Details
In the international open-label trial, 238 patients were randomly assigned between March 2021 and July 2023 to receive pirtobrutinib at 200 mg once daily continuously (n = 119) or investigator choice (n = 119) of IdelaR (n = 82) or BR (n = 37). Patients could cross over from investigator choice to receive pirtobrutinib at disease progression. The primary endpoint was progression-free survival on independent review committee assessment.
Key Findings
Median follow-up was 17.2 months (95% confidence interval [CI] = 9.7–23 months). Median progression-free survival was 14 months (95% CI = 11.2–16.6 months) in the pirtobrutinib group vs 8.7 months (95% CI = 8.1–10.4 months) in the investigator choice group (hazard ratio [HR] = 0.54, 95% CI = 0.39–0.75, P = .0002).
Median time to the next treatment or death was 24 months (95% CI = 17.8–29.7 months) in the pirtobrutinib group vs 10.9 months (95% CI = 8.7–12.5 months) in the investigator choice group (HR = 0.37, 95% CI = 0.25–0.52).
A total of 50 patients in the investigator choice group crossed over to receive pirtobrutinib upon disease progression. The unadjusted HR for overall survival for the pirtobrutinib group vs the investigator choice group was 1.09 (95% CI = 0.68–1.75, P = .7202), with an 18-month rate of 73.4% (95% CI = 63.9%–80.7%) vs 70.8% (95% CI = 60.9%–78.7%).
Grade ≥ 3 adverse events were reported in 57.7% of the pirtobrutinib group vs 73.4% of the investigator choice group; the most common such events in the pirtobrutinib group included pneumonia (15.5%) and neutropenia (14.7%). Adverse events resulted in the discontinuation of treatment in 17.2% vs 34.9% of patients.
The investigators concluded: Pirtobrutinib improved [progression-free survival] and [time to next treatment or death] and demonstrated favorable tolerability, versus IdelaR/BR in exclusively [covalent BTK inhibitor–] pretreated patients with CLL/SLL.”
Jeff P. Sharman, MD, of Willamette Valley Cancer Institute and Research Center, US Oncology Research, Eugene, Oregon, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Eli Lilly and Company. For full disclosures of all study authors, visit the Journal of Clinical Oncology.
