Pacritinib, a JAK2/interleukin-1 receptor─associated kinase inhibitor, is currently under investigation in phase 2 (PAC203) and phase 3 (PERSIST-1 and PERSIST-2) clinical trials as a treatment option for patients with advanced myelofibrosis (MF) who have baseline thrombocytopenia. Patients enrolled in PERSIST-1, PERSIST-2, or PAC203 could apply for compassionate use of pacritinib after the study closed if investigators determined the patient benefitted from the drug and had an unmet medical need without experiencing disease progression or high-grade cardiovascular events. The data presented here focused on those patients who continue pacritinib treatment on a compassionate-use basis after the respective trials were terminated.
A total of 82 patients were approved for compassionate use and 75 received pacritinib (n = 41 from the phase 3 PERSIST-1/PERSIST-2 studies; n = 34 from the PAC203 dose-finding study). Median age at the time of original study enrollment was 69 years (range, 37-84 years). At the time of this analysis, 20 patients continue to receive compassionate-use pacritinib. Dosing data were available in 69 patients: 67% were on 200 mg twice daily, 28% on 100 mg twice daily, and 6% on 100 mg once daily. Dose escalation up to 200 mg twice daily was permitted in 97% of patients treated at lower pacritinib doses during the original trials. Median total treatment duration was 21.1 months (range, 0.8-80.9 months), combining the time periods while on the original study (7.8 months; range, 0-32.9 months) and on the subsequent compassionate-use study (11.6 months; range, 0.3-61.2 months). Prior to initiation of compassionate use, 40% of patients had platelet counts <50 × 109/L, 74% had platelet counts <100 × 109/L, and 52% had hemoglobin levels <10 g/dL. For patients with baseline platelet count <50 × 109/L or with hemoglobin level <10 g/dL, the median treatment duration was similar to the overall population. Patients who were JAK inhibitor naïve had longer median treatment durations (29.4 months) compared with those who had received prior JAK2 inhibitor treatment (18.4 months).
Among the 75 patients who received compassionate-use pacritinib, 44% experienced a serious adverse event, which was more likely related to end-stage MF disease rather than pacritinib treatment. Serious adverse events included infection (13%, n = 10), bleeding (19%, n = 14), cytopenias (4%, n = 3), and heart failure (4%, n = 3). With regard to infections, only 1 was considered atypical or potentially opportunistic (a case of Actinomyces pneumonia occurring in a patient with baseline neutropenia and resolved with antibiotics). There was 1 case of skin cancer in a patient with an extensive history of both squamous- and basal-cell skin cancers.
In conclusion, these findings demonstrate that long-term treatment with pacritinib in patients with advanced MF who have thrombocytopenia and anemia can safely accord further clinical benefit without an additional burden of serious adverse events beyond that observed in earlier studies.
Source: Harrison CN, Yacoub A, Scott BL, et al. Long-term treatment with pacritinib on a compassionate use basis in patients with advanced myelofibrosis. American Society of Hematology Annual Meeting and Exposition; December 11-14, 2021. Abstract 3649.