Outcomes of patients with myelofibrosis treated with compassionate use pacritinib: a sponsor-independent international study

Myelofibrosis (MF) is a chronic yet progressive myeloid neoplasm in which only a minority of patients undergo curative therapy, hematopoietic stem cell transplantation. Ruxolitinib, a JAK1/2 inhibitor, is the lone therapy approved for MF, offering a clear symptom and spleen benefit at the expense of treatment-related cytopenias. Pacritinib (PAC), a multi-kinase inhibitor with specificity for JAK2, FLT3, and IRAK1 but sparing JAK1, has demonstrated clinical activity in MF with minimal myelosuppression. Due to an FDA-mandated full clinical hold, the randomized phase 3 PERSIST trials were abruptly stopped and PAC was immediately discontinued for all patients. Thirty-three patients benefitting from PAC on clinical trial prior to the hold were allowed to resume therapy on an individual, compassionate-use basis. This study reports the detailed outcomes of 19 of these PAC retreatment patients with a median follow-up of 8 months. Despite a median platelet count of 49 × 10⁹/L at restart of PAC, no significant change in hematologic profile was observed. Grade 3/4 adverse events of epistaxis (n = 1), asymptomatic QT prolongation (n = 1), and bradycardia (n = 1) occurred in three patients within the first 3 months of retreatment. One death due to catheter-associated sepsis occurred. The median time to discontinuation of PAC therapy on compassionate use for all 33 patients was 12.2 (95% CI 8.3—NR) months. PAC retreatment was associated with modest improvement in splenomegaly without progressive myelosuppression and supports the continued development of this agent for the treatment of MF second line to ruxolitinib or in the setting of treatment-limiting thrombocytopenia.