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Phase 3 and 2 Trials Highlight Feasibility of Pacritinib in MF
Results on the compassionate use of pacritinib after the phase 3 PERSIST-1, PERSIST-2, and phase 2 PAC203 trials were presented at the 2021 American Society of Hematology (ASH) Annual Meeting to disclose the efficacy and safety of this extended treatment in advanced myelofibrosis (MF), including those with thrombocytopenia and anemia.
“Patients enrolled in PERSIST-1, PERSIST-2, or PAC203 were eligible for compassionate use if they were benefiting from pacritinib in the opinion of the investigator and had an unmet medical need. Patients were excluded if they progressed to acute leukemia or experienced high-grade cardiac or bleeding events on this study,” explained Claire Harrison, DM, Guy’s and St Thomas’ NHS Foundation Trust, United Kingdom, and co-researchers.
Previous studies were unique in the MF landscape due to their enrollment of patients with advanced disease and severe cytopenias with severely limited treatment options. When the studies closed, patients could apply to continue treatment based on a compassionate use basis.
Dosing regimens of compassionate use pacritinib were 200 mg twice daily, 100 mg twice daily, and 100 mg daily. For those treated at lower or intermediate doses during the original clinical trials, dose escalation up to 200 mg twice daily was permitted at the discretion of the medical monitor and treating physician.
Evaluation protocols were set for blood counts and chemistry every 3 months, electrocardiogram every 3 months, and left ventricular ejection fraction every 6 months while on treatment.
In all, 82 patients were approved for compassionate use and 75 received pacritinib. Out of these 75, 41 were originally enrolled in the phase 3 PERSIST studies, and 34 were from the PAC203 dose-finding study.
The median age at the time of original enrollment was 69 years (37-84). Most patients (70%) had received prior JAK2 inhibitor. Approximately half (51%) had baseline peripheral blast count ≥1%. Notably, the baseline platelet count was <50x109/L in 34% of patients and <100 x109/L in 69%, with the baseline hemoglobin level being <10 g/dL in 49%.
“Prior to compassionate use, 40 percent had platelet counts <50x109/L in 69%, 74% had platelet counts <100x109/L, and 52% had hemoglobin <10 g/dL. Among the 69 patients with available data, 67 percent received compassionate use pacritinib at a starting dose of 200 mg BID, 28 percent received 100 mg BID, and 6 percent received 100 mg daily. 97 percent received the same or a higher dose as they had received prior,” continued Dr Harrison and co-authors.
The median total combined duration of treatment with pacritinib was 21.1 months (range 0.8-80.9). Further, the median treatment duration was 7.8 months (0-32.9) on the original study, and 11.6 months for compassionate use (0.3-61.2). For patients with baseline platelet count <50x109/L or with hemoglobin <10 g/dL, the median treatment duration was similar to the overall population.
Nearly half (44%) of patients experienced a serious adverse event (AEs). Most serious AEs were unlikely related to pacritinib and were expected in an end-stage MF population, including infection (13%, n=10), bleeding (19%, n=14), cytopenias (4%, n=3), and heart failure (4%, n=3).
“This analysis demonstrates the feasibility of prolonged treatment with pacritinib in patients with advanced MF, including those with thrombocytopenia and anemia. Reported SAEs were consistent with those previously observed with pacritinib and with the end-stage, compassionate use treatment setting,” concluded Dr Harrison, et al.—Alexa Stoia
Source: Harrison C, Yacoub A, Scott B, et al. Long-Term Treatment with Pacritinib on a Compassionate Use Basis in Patients with Advanced Myelofibrosis. Presented at: the 2021 ASH Annual Meeting; Dec. 11-14; 2021; Abstract 3649.
