Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S382 for hemoglobin improvement vs pacritinib. Keywords: MPN, myelofibrosis, anemia, safety, momelotinib, pacritinib MPN-093 Impact of Transfusion Burden on Health‑Related Quality of Life and Functioning in Patients With Myelofibrosis: Post Hoc Analysis of SIMPLIFY‑1 and ‑2 Ruben Mesa MD1, Francesca Palandri MD, PhD2, Srdan Verstovsek MD, PhD3, Lucia Masarova MD3, Claire Harrison MD, FRCP, PRCPath4, Flora Mazerolle MSc5, Boris Gorsh PharmD6, Manal M’hari MSc5, Zhaohui Wang MS6, Catherine Ellis BA6, Samineh Deheshi PhD7, Jun Kawashima MD7, Robyn von Maltzahn MSc8, Antoine Regnault PhD5 1Wake Forest University School of Medicine, Winston-Salem, USA. 2IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. 3The University of Texas MD Anderson Cancer Center, Houston, USA. 4Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom. 5Modus Outcomes, Lyon, France. 6GSK plc, Philadelphia, USA. 7Sierra Oncology, San Mateo, USA. 8GSK plc, London, United Kingdom Context: Myelofibrosis is associated with substantial symptom burden that can negatively affect health-related quality of life (HRQOL). Although there may be further negative QOL impact in transfusion-dependent (TD) patients, the association between transfusion burden and QOL has not been well characterized. Objective: To characterize the relationship between transfusion burden and patient-reported outcomes (PROs) with an exploratory post hoc analysis of the Phase III SIMPLIFY trials of the JAK1/ JAK2/ACVR1 inhibitor momelotinib in patients with myelofibrosis. Design: The pooled analysis set comprised both arms of the intent-to-treat populations of SIMPLIFY-1 (JAK inhibitor-naïve, momelotinib vs ruxolitinib; N=432) and SIMPLIFY-2 (JAK inhibitor-experienced, momelotinib vs best available therapy; N=156). Definitions were transfusion independent (TI), no transfusions and hemoglobin ≥8 g/dL in 12 weeks; TD, ≥4 units transfused or hemoglobin <8 g/dL in 8 weeks; and transfusion requiring (TR), not meeting TI or TD criteria. PROs were assessed with SF-36v2 (physical functioning [PF], role-physical [RP], general health [GH], vitality [VT], social functioning [SF], and mental health [MH] domains; norm-based score [NBS] ranges vary based on domain). PROs by transfusion status were described over the 24-week randomized period. Results: SF-36v2 NBS were available from 503 of 588 patients at baseline; mean NBS in all domains were lower than the general population mean (50; SD, 10): PF, 39.6; RP, 39.0; GH, 39.8; VT, 43.6; SF, 43.2; and MH, 46.3. Mean NBS in all domains at baseline and week 24 (W24) were lower in TD vs TI patients. Among baseline TD patients (n=150) at W24, 75 remained TD, 40 became TI, 21 became TR, and 14 lacked data. Patients who became TI experienced greater improvement in most domains vs patients who remained TD. Conclusion: Among patients with myelofibrosis in the SIMPLIFY studies, TD patients had lower functioning and HRQOL than TI patients across SF-36v2 domains, suggesting that transfusion dependence negatively affects multiple aspects of QOL. Baseline TD patients who became TI at W24 had greater improvement across most domains than those who remained TD, with mean changes near/above the minimally important differences. These analyses support further research into the impact of transfusions on QOL in myelofibrosis. Keywords: MPN, myelofibrosis, momelotinib, transfusion, anemia, healthrelated quality of life MPN-111 SVR (Spleen Volume Reduction) Predicts OS (Overall Survival) in MF (Myelofibrosis) Patients on PAC (Pacritinib) but Not BAT (Best Available Therapy): PERSIST‑2 Landmark OS Analysis Helen Ajufo MD1, Jan Philipp Bewersdorf MD1, Claire Harrison MD2, Francesca Palandri MD3, John Mascarenhas MD4, Jeanne Palmer MD5, Aaron Gerds MD6, Jean-Jacques Kiladjian MD7, Sarah Buckley MD8, Andriy Derkach PhD1, Karisse Roman-Torres MS8, Raajit Rampal MD1 1Memorial Sloan Kettering Cancer Center, New York, NY, USA. 2Guy’s and St Thomas’ NHS Trust, London, United Kingdom. 3IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia s. Orsola-Malpighi, Bologna, Italy. 4Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 5Mayo Clinic, Phoenix, AZ, USA. 6Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA. 7Hôpital Saint- Louis, Université de Paris, Paris, France. 8CTI BioPharma Corp., Seattle, WA, USA Background: JAK2 inhibitors can reduce spleen volume in MF patients, and SVR is considered a surrogate for disease response. Ruxolitinib (RUX) cannot be administered at full dose in patients with low platelets (PLTs), and it is not known whether SVR is associated with survival benefit in such patients. PAC is a JAK2/ IRAK1/ACVR1 inhibitor that was studied in MF patients with PLTs ≤100×109/L in the PERSIST-2 study, in which PAC demonstrated a significant SVR benefit vs BAT (including RUX). Here we present a retrospective analysis of the relationship between SVR and OS in patients with cytopenic MF. Methods: This analysis includes PERSIST-2 patients in the study at the start of the 12-week SVR window who received PAC 200 mg BID or BAT. OS was evaluated among SVR responders vs non-responders using different SVR thresholds (≥35%, ≥20%, ≥10%, >0%) and a landmark analysis methodology. OS curves were compared using the log-rank test. Results: SVR ≥10% was associated with a significant survival benefit on PAC. This threshold demonstrated the greatest separation in OS curves between responders (n=65) and non-responders (n=24), with no deaths among responders vs 5 among non-responders (P<0.0001). SVR >0% and SVR ≥20% were also associated with improved survival on PAC. While SVR ≥35% is a standard response threshold, it was a less predictive indicator of survival on PAC (P=0.3516), as many patients with SVR <35% were long-
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