Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S404 ruxolitinib (part 2) in patients with MF and suboptimal ruxolitinib response. Main Outcome Measures: Safety/tolerability, including dose-limiting toxicities (DLTs). Results: As of datacut 18Jan2023, 13 patients were treated in part 1 (4mg, n=6; 8mg, n=4; 10mg, n=1; 12mg, n=2); 3 received 4mg+ruxolitinib in part 2 (overall age range, 50–79 years; men, n=9; study treatment duration range, 15–314 days). 12 patients had MF; 4 had MDS/MPN. In part 1, all 6 patients in the 4mg cohort discontinued treatment (3 for progressive disease [PD]; MF, n=2; MDS/MPN, n=1); 1 MF patient discontinued for thrombocytopenia (12mg cohort). The other 9 patients continue treatment. Thrombocytopenia was the most common treatmentemergent adverse event (TEAE; n=9) and the only TEAE leading to discontinuation (n=3). Grade ≥3 TEAEs occurring in ≥1 patient were thrombocytopenia (n=4), anemia (n=3), and hypokalemia (n=2). 8 serious AEs occurred across 4 patients (only COVID-19 occurred in >1 patient [n=2]); all but one (pneumonia) were unrelated to study treatment. There were 2 DLTs (thrombocytopenia [MDS/MPN patient] and hyperbilirubinemia [MF patient]; both 12mg cohort) and 2 deaths (both 4mg cohort due to PD [MF, n=1; MDS/MPN, n=1]). Conclusions: INCB057643 monotherapy (4 and 8mg qd) and combined (4mg qd) with ruxolitinib was generally well tolerated. 12mg qd monotherapy caused 2 DLTs. There were no treatment-related fatal events. Dose finding (part 1) is ongoing with 10mg qd, after which recommended Phase II dose will be declared. Combination dose escalation is also ongoing. Preliminary efficacy will be presented. Sponsorship: Incyte Keywords: MPN, myelofibrosis, myeloproliferative disorder, myelodysplastic syndrome, epigenetic, Phase I MPN-571 Effect of New or Worsening Anemia on Clinical Outcomes in Patients With Myelofibrosis (MF) Treated With Ruxolitinib (RUX): A Post Hoc Analysis of the COMFORT‑I and ‑II Trials Haifa Al-Ali MD1, Ruben Mesa MD2,3, J.E. HamerMaansson MSPH4, Evan Braunstein MD, PhD4, Claire Harrison DM, FRCP, FRCPath5 1Krukenberg Cancer Center, University Hospital of Halle, Halle, Germany. 2Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston Salem, USA. 3Wake Forest University School of Medicine, Winston Salem, USA. 4Incyte, Wilmington, USA. 5Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom Context: Transient dose-dependent anemia is a known consequence of RUX treatment. Objective: Assess impact of new/ worsening anemia induced by RUX on spleen volume response (SVR), symptom severity, and overall survival (OS) in patients with MF. Design: Post hoc analysis of the COMFORT-I/II RUX arms. Patients were categorized by baseline anemia: nonanemic (hemoglobin [Hb] >100g/L), anemic non-transfusion dependent (NTD; Hb <100g/L, received <2 units red blood cells [RBCs]), and anemic transfusion dependent (TD; Hb <100g/L, received ≥2 units RBCs) over 8 (COMFORT-I) or 12 weeks (COMFORTII) before first RUX dose. Outcomes: Percentage of patients with SVR35 (≥35% reduction in spleen volume from baseline; pooled Week 24 and Week 48 COMFORT-I/II data), ≥50% reduction in MF Symptom Assessment Form total symptom score (TSS response; COMFORT-I data), or ≥6.5-point increase in Functional Assessment of Cancer Therapy–Lymphoma total score (FACT-Lym TS response; COMFORT-II data) at Week 24. Outcomes were stratified by presence/absence of new/worsening anemia (Hb decrease ≥15g/L or new transfusion requirement postbaseline until Week 12). OS for each cohort evaluated by Kaplan-Meier methods (P-value per log rank test); other P-values calculated per Fischer exact method. Results: 277 patients were included (nonanemic, 55.6%; NTD, 19.9%; TD, 24.5%). SVR35 rates at Week 24 among patients with, compared to those without, new/worsening anemia were 48.8% vs 43.2% (nonanemic), 33.3% vs 23.1% (NTD), and 41.4% vs 28.2% (TD). Similar results were seen at Week 48. Percentages of patients with TSS response in those with vs without new/worsening anemia were 51.1% vs 42.9% (nonanemic), 42.1% vs 40.0% (NTD), and 46.7% vs 54.2% (TD); percentages with FACT-Lym TS response were 48.6% vs 43.6%, 52.2% vs 50.0%, and 28.6% vs 53.3%, respectively. Median OS was not reached in either group among baseline-nonanemic patients and 50.0 vs 38.4 months (with vs without new/worsening anemia, respectively) among baselineanemic patients. All outcome comparisons between groups were not significant. Conclusions: The onset of new/worsening anemia postbaseline did not diminish clinical benefit of RUX treatment vs patients without new/worsening anemia. RUX was associated with improved spleen volume and symptoms in patients with MF regardless of baseline anemia status. Sponsorship: Incyte Keywords: anemia, JAK inhibitor, MF, myelofibrosis, myeloproliferative disorder, MPN, phase I, phase II MPN-574 Characteristics and Clinical Outcomes in Patients With Polycythemia Vera Receiving Ruxolitinib After Hydroxyurea: A Longitudinal Analysis From the Prospective Observational Study of Patients With Polycythemia Vera in US Clinical Practices Trial (REVEAL) Aaron T. Gerds MD MS1, Michael R. Grunwald MD2, Stephen T. Oh MD PhD3, Evan Braunstein MD PhD4, Zhenyi Xue PhD4, Valkal Bhat PharmD4, Jingbo Yu MD PhD4, Ruben Mesa MD5 1Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA. 2Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA. 3Washington University School of Medicine, St. Louis, MO, USA. 4Incyte Corporation, Wilmington, DE, USA. 5UT Health San Antonio MD Anderson Cancer Center, San Antonio, TX, USA Context: Resistance/intolerance to first-line hydroxyurea occurs in ~24% of patients with polycythemia vera (PV); ruxolitinib is recommended in second-line. Objective: Describe characteristics and outcomes of PV patients receiving ruxolitinib after hydroxyurea
RkJQdWJsaXNoZXIy MTk3NTQxMg==