Hematologic Improvement Experienced By Pacritinib-Treated Patients with Myelofibrosis in Real-World Clinical Settings

Background: Pacritinib (PAC) is a JAK1-sparing inhibitor of JAK2/IRAK1/ACVR1 that can be administered at full dose to patients regardless of baseline platelet count (PLT). While prior studies have shown that PAC is associated with PLT stability and, in some cases, improvement (Vachhani P, et al. Blood. 2023; 142 (Suppl 1):4554; and Marrone M, et al. J Clin Oncol. 2024; 42(16)(Suppl 6579)) real-world evidence is limited. Here, we report treatment outcomes for patients with MF and thrombocytopenia treated with PAC experiencing a PLT 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 PLT <100 x10⁹/L at the time of PAC initiation (index) were included. PLT response was defined as per International Working Group (IWG) criteria: baseline PLT <20 x10⁹/L increasing to >20 x10⁹/L and by at least 100%, or baseline PLT 20-100 x10⁹/L with an absolute increase of ≥30 x10⁹/L within 90 days of starting PAC. Treatment-related outcomes including PLT and hemoglobin levels (Hb) from post-index day 90 through the end of the study period and overall survival (OS) probabilities and 95% confidence intervals from post-index day 90 were estimated for patients achieving a PLT response. Continuous variables were summarized using medians, and interquartile range (IQR), and categorical variables were described using counts and percentages.

Results: Among the 61 patients treated with PAC from 01 June 2022 through 31 August 2023 with PLT <100 x10⁹/L at index and ≥90 days of follow-up, 45.9% (28/61) met the criteria for PLT response by post-index day 90. The median age of patients with a PLT response was 80 years (IQR: 69, 82) at index and the majority of patients were male (64.3%, 18/28) or White (64%, 18/28). The time from MF diagnosis to index was a median of 7.1 months (IQR: 0.1, 35.7), and the median follow-up from index of 8.9 months (IQR: 4.5, 11.5). At index, median PLT count for responders was 64.5 x10⁹/L (IQR: 45.0, 81.0) (n=28) and 89.0 x10⁹/L (IQR: 63.8, 110.0) (n=23) at post-index day 90. Median PLT counts continued to increase from day 90 to day 180 (94.0 x10⁹/L; IQR: 62.0, 119.0) (n=22). Among patients who did not meet the criteria for PLT response by post-index day 90 (n=33), median PLT was 48.0 x10⁹/L (IQR: 30.0, 68.0) at index (n=33) and 51.0 x10⁹/L (IQR: 19.0, 71.0) at day 90 (n=23), and remained stable through day 180 (51.0 x10⁹/L; IQR: 35.0, 67.0) (n=21). Increases in median Hb were observed among patients with a PLT response from index (8.8 g/dL; IQR: 7.4, 10.4) to day 90 (9.4 g/dL; IQR: 7.7, 10.6) (n=23), and through day 180 (9.9 g/dL; IQR: 7.7, 10.7) (n=23). From post-index day 90, 6-month OS was 93.7% (95% CI: 63.2-99.0) among patients with a PLT response, and 82.9% (95% CI: 59.8-93.3) among those not meeting criteria for response.

Conclusions: Almost half of PAC-treated patients with thrombocytopenia experienced a PLT response in this real-world analysis. These patients achieved meaningful increases in not only PLT, but also in Hb. OS was consistent among patients meeting the criteria for PLT response and those who did not.