Pacritinib Approved for Intermediate- or High-Risk Myelofibrosis With Thrombocytopenia

Myelofibrosis stain.

The FDA has approved pacritinib (VonjoTM, CTI BioPharma) for the treatment of adult patients with intermediate- to high-risk primary or secondary myelofibrosis with a platelet count below 50×109/L. Pacritinib is a novel oral kinase inhibitor which inhibits Janus kinase 2 (JAK2) with minimal myelosuppression. Previous treatments available for intermediate- and high-risk myelofibrosis have not been approved for patients with severe cytopenia.

“Pacritinib can provide a treatment option for patients with myelofibrosis and baseline thrombocytopenia, for whom current treatment options are limited,” wrote John Mascarenhas, MD, Professor of Medicine at the Icahn School of Medicine at Mount Sinai, and colleagues, in their publication of the results of the phase 3 PERSIST-2 trial (NCT02055781), on which the approval was based.

This international, multicenter trial randomized 311 patients with myelofibrosis who had a platelet count of 100×109/L or less and palpable splenomegaly in a 1:1:1 ratio to receive 400 mg pacritinib once a day, 200 mg pacritinib twice a day, or best available therapy including ruxolitinib. The coprimary end points were patients achieving spleen volume reduction 35% or more as assessed by computed tomography (CT) or magnetic resonance imaging (MRI) and a reduction in total symptom score of 50% or more at Week 24 as assessed by Myeloproliferative Neoplasms Symptom Assessment Total Symptom Score (MPN-SAF TSS) 2.0. Exploratory end points included overall survival and hematologic parameter changes.

Pacritinib 200 mg twice daily was more effective than best available therapy for reducing splenic volume and total symptom score, with 22% of patients in the pacritinib twice-daily group having splenic volume reduction of 35% or more compared with 3% on best available therapy. Additionally, 32% of patients had a total symptom reduction of 50% or more compared with 14% of patients receiving best available therapy. Pacritinib was effective for patients who had received prior anti-JAK therapy. In addition, pacritinib produced improvements in hemoglobin and reduction in transfusion burden.

In the pacritinib twice-daily group, 9% of patients discontinued therapy due to adverse events.Grade ≥3 thrombocytopenia was experienced by 32% of patients, and 22% experienced grade ≥3 anemia. Nonhematologic adverse events occurring in ≥15% of patients in either pacritinib dosage arm were gastrointestinal adverse events, fatigue, peripheral edema, and dizziness. Serious adverse events experienced by ≥3% of patients in the 200-mg dosing group included anemia, thrombocytopenia, pneumonia, cardiac failure, disease progression, pyrexia, and skin squamous cell carcinoma.

“The symptom benefit of pacritinib in patients with moderate and severe thrombocytopenia is demonstrated in the PERSIST-2 study. A significant reduction in symptoms was observed in patients treated with pacritinib 200 mg [twice daily],” concluded Jeanne M. Palmer, MD, Vice Chair and Section Chief for Hematology at the Mayo Clinic, and colleagues, in a presentation at the 2021 American Society of Hematology Annual Meeting & Exposition. “Furthermore, the modified TSS response rate of 35% in patients treated with pacritinib 200 mg [twice daily] is comparable to that reported for approved JAK1/2 inhibitors in patients with higher platelet counts, suggesting the potential for pacritinib to address the unmet need of patients with cytopenic myelofibrosis.”

The recommended dose of pacritinib is 200 mg orally twice a day. Pacritinib is contraindicated with concomitant use of CYP3A4 inhibitors or inducers.

For More Information

Mascarenhas J, Hoffman R, Talpaz M, et al (2018). Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis: a randomized clinical trial. JAMA Oncol, 4(5):652-659. DOI:10.1001/jamaoncol.2017.5818

Palmer JM, Mesa RA, Oh ST, et al (2021). The impact of pacritinib on myelofibrosis symptoms in patients with moderate and severe thrombocytopenia: a retrospective analysis of patients in the Persist-2 study [poster presentation]. 63rd American Society of Hematology Annual Meeting & Exposition. Abstract 3628. (2021). Pacritinib versus best available therapy to treat patients with myelofibrosis and thrombocytopenia (PAC326). NLM identifier: NCT02055781.

VonjoTM (pacritinib) prescribing information (2022). CTI BioPharma Corp. Available at: (2022). CTI BioPharma announces FDA accelerated approval of VONJOTM (pacritinib) for the treatment of adult patients with myelofibrosis and thrombocytopenia. Available at:

Image credit: El*Falaf. Licensed under CC-BY-SA 4.0

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