Early Anemia Response in Patients with Myelofibrosis Treated with Pacritinib in Real-Word Clinical Settings

Background: Anemia presents a significant burden to patients with myelofibrosis (MF) including need for transfusions affecting quality of life and prognosis. Pacritinib (PAC), a JAK1-sparing inhibitor of JAK2/IRAK1/ACVR1, has demonstrated a clinical and statistically significant improvement in transfusion requirements for patients with MF who are not transfusion-independent at baseline in post-hoc analyses of the phase 3 PERSIST-2 study (Oh S, et al. Blood Adv. 2023; 7(19)). Emerging real-world evidence suggests PAC is associated with early hemoglobin (Hb) improvements in some patients (Marrone M, et al. J Clin Oncol. 2024; 42(16)(Suppl 6579)). This observation may be attributed to PAC's unique kinome profile as an ACVR1 inhibitor, with the ability to be delivered at full dose regardless of cytopenias. The current study evaluates outcomes for patients treated with PAC with an early anemia response in real-world clinical practice.

Methods: Integra-PrecisionQ database, a de-identified harmonized dataset including electronic health data and practice management data (roughly 80% community oncology practices) was used for this retrospective observational study. Patients diagnosed with MF treated with PAC between 01 June 2022 and 31 August 2023 with anemia (Hb <10 g/dL) at the time of PAC initiation (index) were included. Anemia response was defined as an absolute increase in Hb of ≥1.5 g/dL within 90 days of treatment with PAC. Outcomes including Hb and platelet counts (PLT) from post-index day 90 through the end of the study period were described for patients with a response overall, and by baseline Hb levels (Hb <8.0 g/dL, and 8 to 10 g/dL). Continuous variables were summarized using medians, and interquartile range (IQR), and categorical variables were described using counts and percentages.

Results: A majority of patients achieving Hb response were severely anemic (Hb <8.0 g/dL) at index (68%; 17/25), and 32% (8/25) had moderate anemia (Hb 8.0 to 10 g/dL) at index. For patients with severe anemia at index achieving an Hb response, median Hb (IQR) was 7.2 g/dL (6.5, 7.7) at index (n=17), and 8.0 g/dL (7.1, 8.8) at day 90 (n=15) and remained stable at day 180 (7.7 g/dL; IQR: 6.9, 8.3) (n=13). For patients with moderate anemia, median Hb (IQR) at index was 8.5 g/dL (8.3, 8.7) (n=8), and 9.3 g/dL (9.0, 10.6) at day 90 (n=5) and 9.3 g/dL; IQR: 9.0, 10.6) (n=5) at day 180. Median PLT counts improved among patients with severe anemia from index (72.0 x10⁹/L; IQR: 52.0, 179.0) (n=17), through day 90 (76.5 x10⁹/L; IQR: 57.4, 127.0) (n=16), and day 180 (101.0 x10⁹/L; IQR: 58.0, 133.0) (n=13). Similar improvements in median PLT were observed among patients with moderate anemia from index (68.0 x10⁹/L; IQR: 30.8, 116.0) (n=8), through day 90 (107.0 x10⁹/L; IQR: 67.0, 137.0) (n=5), and day 180 (94.0 x10⁹/L; IQR: 62.0, 109.0) (n=5).

Conclusions: The majority of patients who had anemia at the time of treatment initiation experienced an early anemia response with PAC treatment which was maintained over the follow up period. Meaningful improvements in Hb and PLT counts over follow up were observed overall and across categories of baseline Hb.

Mascarenhas:Disc: Consultancy; Ajax: Research Funding; Novartis: Consultancy, Other: Travel Support , Research Funding, Speakers Bureau; Karyopharm: Consultancy; GSK: Consultancy; Keros: Consultancy; Celgene: Consultancy, Other: Travel Support, Speakers Bureau; Icahn School of Medicine at Mount Sinai: Current Employment; Kartos: Consultancy, Research Funding; Geron: Consultancy, Research Funding; Sumitomo: Consultancy; PharmaEssentia: Consultancy, Research Funding; Merck: Consultancy; Pfizer: Research Funding; MorphoSys: Consultancy; Blueprint Medicines: Consultancy; AbbVie: Consultancy, Research Funding; CTI BioPharma/SOBI: Consultancy, Research Funding; Roche: Consultancy; Bristol Myers Squibb: Research Funding; Ariad: Speakers Bureau; NS Pharma: Research Funding; Incyte Corporation: Consultancy, Speakers Bureau; Astellas: Research Funding. Marrone:Sobi Inc.: Current Employment. Morere:IntegraConnect, PrecisionQ: Current Employment. Oladapo:Sobi, Inc.: Current Employment. Suthar:Sobi Inc.: Current Employment, Other: received payment of unvested equity awards as a company employee as part of an overall compensation package from CTI BioPharma Corp., A Sobi company. Sura:IntegraConnect, PrecisionQ: Current Employment. Vasudevan:PQ, IntegraConnect LLC: Current Employment. Vredenburg:Sobi Inc.: Current Employment. Zeng:IntegraConnect, PrecisionQ: Current Employment. Rampal:Blueprint: Consultancy; CTI BioPharma: Consultancy; AbbVie: Consultancy; Incyte Corporation: Consultancy, Research Funding; Karyopharm: Consultancy; Disc Medicine: Consultancy; Stemline Therapeutics: Consultancy, Research Funding; Celgene/BMS: Consultancy; Jubilant: Consultancy; PharmaEssentia: Consultancy; Constellation/MorphoSys: Consultancy, Research Funding; Galecto: Consultancy; Jazz Pharmaceuticals: Consultancy; Ryvu: Research Funding; Zentalis: Consultancy, Research Funding; Servier: Consultancy; Kartos: Consultancy; Sumitomo Dainippon: Consultancy; Cogent: Consultancy; Protagonist: Consultancy; Sierra Oncology/GSK: Consultancy; Novartis: Consultancy; Promedior: Consultancy.