Real-world experience with pacritinib for patients with myelofibrosis refractory to ruxolitinib: a report of three cases

Abstract

Objectives: Ruxolitinib, a Janus kinase (JAK) inhibitor, can lead to severe ruxolitinib discontinuation syndrome (RDS) upon abrupt cessation in myelofibrosis (MF). Pacritinib, a selective JAK2/IRAK1 inhibitor with minimal JAK1 inhibition, offers an alternative, particularly for patients with thrombocytopenia. This case report presents our experience of successfully switching from ruxolitinib to pacritinib in patients with MF and severe RDS.

Case presentation: Three males in their early 20s, 60s, and 70s of Arab ethnicity presented with diverse clinical presentations, including post-polycythemia vera MF, primary MF, and primary triple-negative MF with multiple comorbidities. Ruxolitinib discontinuation was carefully managed through gradual tapering, concurrent corticosteroid administration, and pacritinib initiation, effectively preventing withdrawal syndrome. All patients demonstrated significant clinical improvements with pacritinib. Notable outcomes included reductions in spleen size (ranging from 7 to 8 cm within 1-6 months), stabilization or improvement in hematologic parameters, and resolution of transfusion dependency in previously transfusion-dependent cases. One patient achieved transfusion independence within six months of treatment, while another exhibited marked symptom relief and improved quality of life within one month. Adverse events, including gastrointestinal symptoms, weight loss, and transient voice changes, were manageable through dose adjustments and supportive care, enabling continued therapy.

Conclusion: Our cases contribute to the growing body of evidence supporting pacritinib's role in the evolving treatment landscape of MF.

Keywords: JAK inhibitors; Myelofibrosis; Pacritinib; ruxolitinib discontinuation syndrome; spleen volume reduction; thrombocytopenia.