Comparison of Bleeding-Related Events in Patients Who Received Pirtobrutinib With and Without Antithrombotic Agents

Introduction: Bruton tyrosine kinase inhibitors (BTKi) are associated with increased risk of bleeding events. Pirtobrutinib, a non-covalent (reversible) BTKi FDA approved for treatment of R/R MCL after 2 lines of therapy including a BTKi, demonstrated efficacy and tolerability across B-cell malignancies. Bleeding events in pts treated with pirtobrutinib and concomitant antithrombotic therapy have not been specifically reported. We analyze bleeding events in pts from BRUIN who received pirtobrutinib with antithrombotic therapy. Methods: Pts with B-cell malignancies (317 CLL, 166 MCL, 290 other) enrolled in open-label, multicenter Phase 1/2 BRUIN were analyzed. Concomitant antithrombotic therapy (direct factor XA inhibitors, heparin anticoagulants, platelet aggregation inhibitors) at time of enrolment was permitted (excluding warfarin). Pirtobrutinib was administered QD (28-day cycles) until disease progression/discontinuation due to toxicity. CTCAE V5.0 determined grade and type of bleeding events. Descriptive analyses were performed. Results: 773 pts (29 July 2022) received at least 1 pirtobrutinib dose; 216 with concomitant antithrombotic therapy (median age: 72 years [IQR 65-77]; % ≥75 years: 34%). Median time on pirtobrutinib with and without antithrombotic therapy: 10.6 (IQR 4.0–19.9) and 9.3 months (IQR 3.1–17.3). Any-grade bleeding events were reported in 44.9% (97/216) pts with antithrombotic therapy vs 32.5% (181/557) without. A summary of bleeding events is shown (Table). Most (>90%) were grade ≤2. Most common bleeding events (≥3%) in pts with antithrombotic therapy were contusion (22.7%), hematuria (5.6%), epistaxis (5.1%), petechiae (3.7%), hematoma (3.2%). Of 6 (2.8%) pts on antithrombotic therapy with grade 3 bleeding event, 2 (0.9%) were deemed related to pirtobrutinib by investigators: upper GI bleeding with anemia and hemarthrosis from a knee injury (1 each). Grade ≥3 bleeding events occurred in 11 (2%) pts not taking antithrombotics. Any-grade hemorrhage/hematoma occurred in 13/79 (16.5%) pts who received direct factor XA inhibitors, 10/39 (25.6%) who received heparins, 18/112 (16.1%) who received platelet aggregation inhibitors (some >1 class). Among pts with antithrombotic therapy, median time to onset of any-grade bleeding event was 8.1 weeks (IQR 2.6–24) and median duration of a bleeding event was 2.1 weeks (IQR 0.6-4.3). Among pts who received antithrombotic therapy, bleeding events required dose interruption of pirtobrutinib in 5 pts (2.3%) and no bleeding events led to dose reduction/permanent discontinuation of pirtobrutinib. Conclusion: Concomitant antithrombotic therapy with pirtobrutinib was associated with increased rate of bleeding events vs pirtobrutinib alone; most events were grade ≤2. High-grade bleeding events were infrequent (<2%). This supports safety of pirtobrutinib in pts requiring antithrombotic therapies. Encore Abstract - previously submitted to EHA 2023 The research was funded by: [email protected] Keyword: Other Conflicts of interests pertinent to the abstract W. Jurczak Consultant or advisory role Janssen, Astra Zeneca, Mei Pharma, Lilly, Takeda, Roche, Abbvie, Beigene Research funding: Abbvie, Bayer, Beigene, Celgene, Janssen, Roche, Takeda, TgTherapeutics,Astra Zeneca, Mei Pharma, Lilly N. Lamanna Consultant or advisory role Abbvie, AstraZeneca, Bei-Gene, Genentech, Janssen, Pharmacyclics Research funding: Abbvie, AstraZeneca, Be-Gene, Genentech, Loxo/EliLilly, MingSight, Octapharma, Oncternal, TG Therapeutics C. S. Tam Honoraria: Janssen, AbbVie, Beigene, LOXO, AstraZeneca Research funding: Janssen, AbbVie, Beigene A. Kontos Employment or leadership position: [email protected] Stock ownership: [email protected] H. Konig Employment or leadership position: [email protected] Stock ownership: [email protected] A. S. Ruppert Employment or leadership position: Eli Lilly and Company Stock ownership: Eli Lilly and Company D. E. Tsai Employment or leadership position: [email protected] Stock ownership: [email protected]