Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S520 unnecessary surgical interventions and transfusions. Physicians should be aware of this condition to optimize the management of patients with bleeding disorders of unknown origin. Keywords: plasminogen activator inhibitor 1, antifibrinolytic agent, case CT-166 Long‑Term Safety With ≥12 Months of Pirtobrutinib in Relapsed/Refractory B‑Cell Malignancies Catherine E. Muehlenbein PhD1, Catherine C. Coombs MD2, Nirav N. Shah MD3, Wojciech Jurczak MD, PhD4, Jennifer Woyach MD5, Chan Y. Cheah MD6, Krish Patel MD7, Kami Maddocks MD5, Yucai Wang MD, PhD8, Chunxiao Wang PhD9, Sarang Abhyankar MD1, Donald E. Tsai MD, PhD1, Toby A. Eyre MBChB, DipMedEd, MRCP, FRCPath, MD10 1Loxo@Lilly, Indianapolis, USA. 2UCI Health, Orange, CA, USA. 3Medical College of Wisconsin, Milwaukee, WI, USA. 4Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland. 5The Ohio State University Comprehensive Cancer Center, Columbus, USA. 6Linear Clinical Research and Sir Charles Gairdner Hospital, Perth, Australia. 7Center for Blood Disorders and Cellular Therapy, Swedish Cancer Institute, Seattle, WA, USA. 8Division of Hematology, Mayo Clinic, Rochester, MN, USA. 9Eli Lilly and Company, Indianapolis, USA. 10Oxford University Hospitals NHS Foundation Trust, Churchill Cancer Center, Oxford, USA Context: While Bruton tyrosine kinase inhibitors (BTKis) can induce sustained remissions, ongoing response requires continuous treatment, and thus, long-term safety/tolerability is critical for adherence, maintaining dose intensity, and delivering maximum efficacy. Pirtobrutinib is a highly selective, non-covalent (reversible) BTKi approved by the US Food and Drug Administration in January 2023 for relapsed/refractory (R/R) mantle cell lymphoma after 2 prior lines of therapy including a BTKi. Pirtobrutinib has demonstrated promising efficacy with low discontinuation and dose reduction rates in patients with multiple subtypes of R/R B-cell malignancies. However, the long-term safety and tolerability of pirtobrutinib has not yet been reported. Here we report the clinical safety in patients with long-term (≥12 months) pirtobrutinib treatment from the Phase I/II BRUIN trial. Design and Setting: Patients with R/R B-cell malignancies who received ≥12 months of pirtobrutinib were included. Median time to onset, dose reduction, discontinuation, and cumulative incidence rates were determined for treatment-emergent adverse events (TEAEs) that occurred in ≥20% of patients and select adverse events (AEs) of interest associated with BTKi. Results: As of July 29, 2022, 773 patients were enrolled, and 326 (42%) received treatment for ≥12 months. Among these 326 patients, median time on treatment was 19 months (interquartile range: 16-25), with 231 (71%) remaining on pirtobrutinib. The most common TEAEs (all grade, regardless of attribution) in this long-term 326-patient cohort were fatigue (32%), diarrhea (31%), COVID-19 (29%), contusion (26%), cough (25%), and back pain (21%). TEAEs leading to dose reduction or discontinuation occurred in 23 (7%) and 11 (3%) patients, respectively. Four (1%) patients discontinued due to a treatment-related AE (TRAE), and 1 patient had a fatal TRAE (COVID-19 pneumonia). Comprehensive safety analyses describing the frequency of TEAEs over time will be presented. Conclusion: Prolonged pirtobrutinib therapy continues to demonstrate a safety profile amenable to long-term administration at the recommended dose without evidence of new or worsening toxicity signals. The safety and tolerability observed in patients on therapy for ≥12 months was similar to previously published safety analyses on all patients enrolled regardless of follow-up. To be presented at ASCO 2023. Keywords: CT, B-cell malignancies, Bruton tyrosine kinase inhibitors CT-168 Comparison of Bleeding‑Related Events in Patients Who Received Pirtobrutinib With and Without Antithrombotic Agents Heiko Konig PhD, MD1, Constantine S. Tam MBBS, MD2,3, Nicole Lamanna MD4, Wojciech Jurczak MD5, Arrin Kontos PharmD, RPh1, Amy S. Ruppert PhD6, Donald E. Tsai MD, PhD1 1Loxo@Lilly, Indianapolis, USA. 2Alfred Health, Melbourne, Victoria, Australia. 3Monash University, Melbourne, Victoria, Australia. 4Herbert Irving Comprehensive Cancer Center, Columbia University, New York, USA. 5Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland. 6Eli Lilly and Company, Indianapolis, USA Introduction: Pirtobrutinib, a non-covalent (reversible) Bruton tyrosine kinase inhibitor (BTKi) FDA-approved for treating relapsed/refractory mantle cell lymphoma (R/R MCL) after 2 lines of therapy including a BTKi, demonstrated efficacy and tolerability across B-cell malignancies. Bleeding events (BEs) in patients treated with pirtobrutinib and concomitant antithrombotic therapy (CAT) have not been reported. We analyze bleeding events in patients from BRUIN who received pirtobrutinib with antithrombotic therapy. Methods: Patients with B-cell malignancies (317 CLL, 166 MCL, 290 other) enrolled in open-label, multicenter phase 1/2 BRUIN, who received pirtobrutinib with CAT were analyzed for BEs. CAT (direct-factor XA inhibitors, heparin anticoagulants, platelet aggregation inhibitors) at the time of enrollment was permitted (excluding warfarin). Pirtobrutinib was administered QD (28-day cycles) until disease progression/discontinuation from toxicity. CTCAE V5.0 determined the grade and type of BEs. Descriptive analyses were performed. Results: 773 patients (data cut-off of 29 July 2022) received ≥1 pirtobrutinib dose; 216 with CAT (median age 72 years [IQR 65-77]). Median time on pirtobrutinib with and without CAT was 10.6 (IQR 4.0-19.9) and 9.3 months (IQR 3.1-17.3). Any-grade BEs were reported in 44.9% patients with CAT vs 32.5% (181/557) without. A total of >90% were grade≤2. Common BEs in patients with CAT were contusion (22.7%), hematuria (5.6%), epistaxis (5.1%), petechiae (3.7%), and hematoma (3.2%). Of those using CAT, 2 (0.9%) grade 3 BEs were deemed pirtobrutinibrelated (upper GI bleeding with anemia and hemarthrosis from a knee injury). Eleven patients (2%) without CAT had grade ≥3 BEs. Hemorrhage/hematoma occurred in 13/79 (16.5%), 10/39 (25.6%), and 18/112 (16.1%) patients who received direct factor
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