Real-Word Effectiveness of Pacritinib in Patients with Myelofibrosis Who Have Thrombocytopenia and Anemia
Authors: Rampal Raajit , Marrone Michael , Morere Lisa , Oladapo Abiola , Suthar Purvi , Sura Teena , Vasudevan Anupama , Vredenburg Michael , Zeng Jia , Mascarenhas John O. 
Published: December 2024

Background: The co-occurrence of thrombocytopenia and anemia (bicytopenia) in patients with myelofibrosis (MF) is a therapeutic challenge because of treatment-related myelosuppression from JAK1/2 inhibitors. Pacritinib (PAC) is a JAK1-sparing inhibitor of JAK2/IRAK1/ACVR1 that can be administered at full dose, yielding consistent efficacy, regardless of baseline platelet count (PLT) or hemoglobin levels (Hb) (Gagelmann N. Clin Lymphoma Myeloma Leuk. 2024; S2152-2650(24)00246-5). Recent post-hoc data from the phase 3 PERSIST-2 study have shown that PAC is associated with spleen volume reduction, symptom benefit, and reduced transfusions in patients with bicytopenia (Vachhani P, et al. J Clin Oncol. 2024; 42(16)(Suppl 6578)). The current study evaluated hematologic outcomes and survival in real-world clinical practice, among PAC treated patients with MF who presented with bicytopenia at the time of PAC initiation.
Methods: Integra-PrecisionQ database of de-identified electronic health data and practice management data (roughly 80% community oncology practices) was used for this retrospective observational study of patients with MF and bicytopenia treated with PAC between 01 June 2022 and 31 August 2023. Patients were included in this analysis if they had PLT &lt;100 x109/L and Hb &lt;8.0 g/dL at the time of PAC initiation (index). PLT count and Hb level at baseline and 30-day intervals post-index are reported overall and for a subset of patients with severe bicytopenia (i.e. PLT &lt;50 x109/L and Hb &lt;8.0 g/dL). Overall survival (OS) was assessed from the time of PAC initiation through the end of the study observation period (October 2023), and 12-month survival probabilities and corresponding 95% confidence intervals (CI) were estimated using the Kaplan Meier method. Continuous variables were summarized using medians and interquartile range (IQR), and categorical variables were described using counts and percentages.
Results: Overall, 119 patients with MF treated with PAC from June 2022 and August 2023 had PLT and Hb at index and follow-up. Of the patients with bicytopenia at index (23/119; 19.3%), a majority were male (56.6%, 13/23) with a median (IQR) age at MF diagnosis of 75 years (68, 81), and a median of 5 months (2, 9) of follow-up. Among patients with bicytopenia, median PLT count improved from index (61.0 x109/L; IQR: 36.5, 71.7) (n=23) to day 90 (68.0 x109/L; IQR: 38.0, 82.0) (n=13), and remained stable through day 180 (60.5 x109/L; IQR: 46.3, 97.3) (n=12). Improvement in median Hb was also observed from index (7.2 g/dL; IQR: 6.9, 7.6) (n=23) to day 90 (8.0 g/dL; IQR: 6.9, 8.9) (n=14), and day 180 (7.5 g/dL; IQR: 6.4, 8.8) (n=14). Among the subset of patients with severe bicytopenia (n=8), median PLT count increased from index (27.5 x109/L; IQR: 21.8, 34.3) to day 90 (34.5 x109/L; IQR: 18.3, 47.8) (n=6), and day 180 (42.5 x109/L; IQR: 26.8, 56.0) (n=6). Similarly, median Hb levels improved from index (7.4 g/dL; IQR: 7.0, 7.6) to day 90 (8.1 g/dL; IQR: 6.6, 8.9) (n=6), and day 180 (8.1 g/dL; IQR: 6.6, 8.9) (n=6). OS from index was 77.8% (95% CI: 54.5-90.1) at 6 months in the overall bicytopenia group and 75.0% (95% CI: 31.5-93.1) at 12 months in patients with severe bicytopenia.
Conclusions: Patients with MF who have both thrombocytopenia and anemia treated with PAC in real-world clinical settings experienced improvement or stability in PLT and Hb with similar hematologic improvements observed in patients with severe thrombocytopenia and severe anemia. Real-world OS observed in this subgroup analysis of patients known to have a poor prognosis is comparable with 12-month OS of 69% noted in the full group of PAC treated MF patients (Marrone M, et al. J Clin Oncol. 2024; 42(16)(Suppl 6579)). These results suggest PAC may have clinical utility in addressing unmet needs of patients with MF who have bicytopenias.