Pirtobrutinib in Post-cBTKi CLL/SLL: ~30 Months Follow-up and Subgroup Analysis With/Without Prior BCL2i from the Phase 1/2 BRUIN Study

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.325-325
• Main Authors: Woyach, Jennifer A., Brown, Jennifer R., Ghia, Paolo, Roeker, Lindsey E., Patel, Krish, Eyre, Toby A., Munir, Talha, Lech-Maranda, Ewa, Lamanna, Nicole, Tam, Constantine S., Seymour, John F., Tessoulin, Benoit, Shah, Nirav N., Ujjani, Chaitra S, Fakhri, Bita, Coombs, Catherine C., Flinn, Ian W., Patel, Manish, Nasta, Sunita D., Cohen, Jonathon B., Alencar, Alvaro J., Cheah, Chan Y., Ma, Shuo, Rhodes, Joanna M., Jagadeesh, Deepa, Zinzani, Pier Luigi, Osterborg, Anders, Izutsu, Koji, Tsai, Donald E., Abada, Paolo, Balbas, Minna, Li, Jian, Ruppert, Amy S., Jurczak, Wojciech, Wierda, William G.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-185852

Background: The treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has benefited from covalent (c) Bruton tyrosine kinase inhibitors (BTKi), however, therapy can fail due to progression or intolerance. Sequential treatment with B-cell lymphoma 2 protein inhibitor (BCL2i) venetoclax, either as monotherapy or combined with an anti-CD20 monoclonal antibody, has been the primary treatment option for CLL/SLL patients (pts) whose disease has progressed on cBTKi. Pirtobrutinib is a highly selective, non-covalent (reversible) BTKi that demonstrated promising efficacy in patients with relapsed or refractory CLL/SLL (Mato et al, NEJM, 2023). Here, we report on the efficacy of pirtobrutinib treatment in CLL/SLL in the post-cBTKi setting, including subgroups with or without prior BCL2i, using data from the BRUIN study (NCT03740529) with more than 2 years follow-up. Methods: Pts with previously treated CLL/SLL were eligible for treatment with pirtobrutinib in the multicenter Phase 1/2 BRUIN study. Key endpoints included ORR (including partial response with lymphocytosis; PR-L) as assessed by an independent review committee per 2018 iwCLL response criteria, DoR, PFS, OS, and safety. A data cut of 05MAY2023 was utilized. Results: In total, 282 pts with CLL/SLL who received prior cBTKi were included in this analysis. Median age was 69 years (range, 36-88), 68% were male, and median number of prior therapies was 4 (range, 1-11). Of 282 pts, 154 (55%) had not received prior-BCL2i therapy (Naïve; BCL2i-N) and 128 (45%) had (Exposed; BCL2i-E). BCL2i-N pts were exposed to fewer prior therapies than BCL2i-E pts (median prior therapies 3 and 5, respectively), including anti-CD20 antibody (83% and 97%), chemotherapy (74% and 89%), PI3K inhibitor (11% and 42%), CAR-T cell therapy (1% and 12%), and hematopoietic cell transplantation (1% and 6%). The ORR for all post-cBTKi pts was 72% (95% CI, 66.4-77.1), and ORR including PR-L was 82% (95% CI, 76.5-85.9). Post-cBTKi pts included a subgroup of 19 pts with one prior line of cBTKi-containing therapy and second line therapy of pirtobrutinib, who had ORR including PR-L of 89.5% (CI 95%, 66.9-98.7). The ORR including PR-L was 83.1% (95% CI, 76.2-88.7) for BCL2i-N pts, and 79.7% (95% CI, 71.7-86.3) for BCL2i-E pts. Median DoR was 18.4 months (95% CI, 15.3-20.4) for all cBTKi pre-treated pts, 24.9 months (95% CI, 18.4-32.0) for BCL2i-N, and 14.8 months (95% CI, 12.0-17.4) for BCL2i-E. With a median follow up of