Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S392 molecule BETi with dose-proportional pharmacokinetics, linear increases in exposure, and time- and dose-dependent modulation of BET target gene expression. CA011-023 (NCT04817007) is a Phase I/II study evaluating BMS‑986158+RUX or FED in MF. Design: CA011-023 dose escalation comprises BMS-986158+RUX in RUXnaïve patients (Part 1A; first-line [1L] MF) or BMS-986158+FED in RUX-exposed patients (Part 1B; second-line MF). Primary objectives are safety, tolerability, and maximum tolerated dose and/or recommended Phase II dose. Secondary objectives include spleen volume reduction (SVR). JAK2 variant allele frequency is an exploratory assessment. Results: As of 02Sep2022, 11 patients in Part 1A (median age 67 [range, 36–81]) and 12 in Part 1B (median age 69 [range, 37–77]) were treated. Any-grade treatment-related adverse events (TRAEs) occurred in 9 (82%) patients in Part 1A and 9 (75%) in Part 1B. Grade 3/4 TRAEs in Part 1A were thrombocytopenia (n=5, 45%), neutropenia, hypertension, and anemia (n=1 each, 9%), and in Part 1B were thrombocytopenia, anemia (n=5 each, 42%), diarrhea, and blood bilirubin increase (n=1 each, 8%). Dose- limiting toxicities occurred in 2 patients in Part 1A (2.0 and 3.75 mg BMS-986158; both thrombocytopenia) and 3 in Part 1B (1.25 mg BMS-986158; diarrhea, thrombocytopenia, elevated bilirubin). No discontinuations due to TRAEs occurred in Part 1A. SVR was observed at Week 12 in all evaluable patients in Part 1A and continued to deepen at Week 24. In Part 1A, 5/6 and 6/6 patients receiving BMS-986158 (2.0 or 3.0 mg)+RUX met SVR35 at Weeks 12 and 24, respectively. In Part 1B, 0/6 and 1/3 patients receiving BMS-986158 (0.5 or 0.75 mg)+FED met SVR35 at Weeks 12 and 24. Reductions in JAK2V617F frequency were observed in Part 1A (35% max reduction by Cycle 10, n=4) and Part 1B (22% max reduction by Cycle 7, n=2). Conclusion: BMS-986158+RUX or FED had manageable safety profiles with reversible on-target thrombocytopenia; most TRAEs were grade 1/2. Initial results demonstrate robust SVR with BMS-986158+RUX in patients with 1L MF; responses deepened beyond Week 12 under continued treatment. The trial is ongoing; dose expansion is open for enrollment. Keywords: MPN, myelofibrosis, BETi, JAKi, ruxolitinib, fedratinib MPN-383 Healthcare Resource Utilization and Costs Associated With Transfusion Dependence and Anemia Severity in Patients With Myelofibrosis: A Retrospective Analysis of the Medicare Fee‑for‑Service Claims Data Aaron T. Gerds MD, MS1, Joseph Tkacz MS2, Laura Moore-Schlitz PhD2, Jill Schinkel MS2, Kelesitse Phiri ScD, MS3, Tom Liu MS3, Boris Gorsch PharmD3 1Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA. 2Inovalon, Bowie, MD, USA. 3GSK plc, Philadelphia, PA, USA Context: Anemia and transfusion burden among patients with myelofibrosis are substantial drivers of healthcare resource utilization (HCRU) and costs, encompassing inpatient/outpatient medical costs, emergency department (ED) visits, pharmacy costs, and other medical expenses. Objective: To describe patient characteristics, HCRU, and costs for patients with myelofibrosis based on anemia severity and transfusion status in the US Medicare population. Methods: This retrospective cohort study used Medicare fee-forservice data for patients with myelofibrosis between January 1, 2011 and December 31, 2020. The myelofibrosis diagnostic index date (MFDID) was defined as the earliest of 1 inpatient or 2 outpatient claims for myelofibrosis (on separate dates within 90 days). Anemia was defined using claims or laboratory data (hemoglobin <12 g/dL) beginning 100 days before and any time after the MFDID (earliest evidence of anemia was the anemia index date [AID]). Anemia severity was defined as mild (hemoglobin 10–<12 g/dL), moderate (8–<10 g/dL), or severe (<8 g/dL). Transfusions were assessed over a 180-day landmark period following AID; cohorts were defined as transfusion independent (TI; no transfusions), transfusion dependent (TD; ≥6 claims for transfusion on 6 separate days over any 12-week window), or transfusion requiring (TR; received transfusion but did not meet TD criteria). Per patient per month (PPPM) HCRU and costs were compared among transfusion- and anemia-severity cohorts. Results: A total of 1749 patients were included: 980 TI, 559 TR, and 210 TD; mean age, 74.8 years; male sex, 47.9%; White, 81.7%; median Deyo-Charlson Comorbidity Index, 2.0. Greater all-cause outpatient, inpatient, ED, and post–acute care utilization and costs were observed in the TR and TD cohorts. Mean hospitalizations and percentage of cohorts with ≥3 visits (PPPM): 0.13, 28.4% (TI); 0.25, 37.4% (TR); 0.29, 41.0% (TD). Mean ED visits (PPPM): 0.13 (TI), 0.21 (TR), 0.21 (TD). Mean total costs (PPPM): medical, $5830 (TI), $11 130 (TR), $11 337 (TD); pharmacy, $2361 (TI), $3119 (TR), $3318 (TD). In 265 patients with hemoglobin data, incremental increases in HCRU and costs with increasing anemia severity were also observed. Conclusions: Achieving transfusion independence in patients with myelofibrosis may minimize healthcare costs and reduce financial burdens for patients and healthcare systems. Keywords: MPN, myelofibrosis, transfusion, anemia, healthcare resource utilization MPN-386 The Role of Variants of Uncertain Significance From NGS Data for Patients With pH‑Negative Myeloproliferative Neoplasms Anna Kirienko PhD1, Darya Kustova MS1, Ekaterina Motyko PhD1, Elizaveta Efremova MD1, Elena Morozova MD, PhD2, Dzhariyat Shikhbabaeva MD, PhD3, Olga Vinogradova MD3, Vasily Shuvaev MD, PhD1,4, Sergey Sidorkevich MD1, Irina Martynkevich PhD1 1Russian Scientific Research Institute of Hematology and Transfusiology of the Federal Medical-Biological Agency, Saint Petersburg, Russian Federation. 2RM Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Saint Petersburg, Russian Federation. 3State Budgetary Institution of Healthcare of the City of Moscow Clinical Hospital named after SP Botkin of the Moscow City Healthcare Department, Moscow, Russian Federation. 4Russian Medical Academy of Postgraduate Education, Moscow, Russian Federation
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