Pacritinib Granted Accelerated Approval for Use in Myelofibrosis With Severe Thrombocytopenia

In February 2022, the FDA granted accelerated approval to pacritinib for patients with severe thrombocytopenia.

Patients with intermediate- or high-risk primary or secondary myelofibrosis with a low platelet count may derive benefit from treatment with pacritinib following its accelerated approval by the FDA.

Pacritinib (Vonjo) received accelerated approval from the FDA at a twice daily, 200-mg dose for patients with intermediate- or high-risk primary or secondary myelofibrosis who are experiencing severe thrombocytopenia with a platelet count below 50 × 109/L, according to a press release from CTI BioPharma Corporation.1

The agency’s decision comes from results of the phase 3 PERSIST-2 study (NCT02055781).

Treatment with pacritinib at 200 mg resulted in a reduction in spleen volume of at least 35% for 29% of patients, vs 3% of patients who received the best available therapy, including ruxolitinib (Jakafi). As part of the post-approval plans for pacritinib, the phase 3 PACIFICA trial (NCT03165734) will be completed with results estimated in 2025.

“Today's approval of Vonjo establishes a new standard of care for myelofibrosis patients suffering from cytopenic myelofibrosis,” John Mascarenhas, MD, associate professor of medicine, hematology and medical oncology at Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, said in a press release. “Myelofibrosis with severe thrombocytopenia, defined as blood platelet counts below 50 × 109/L, has been shown to result in poor survival outcomes coupled with debilitating symptoms. Limited treatment options have rendered this disease as an area of urgent unmet medical need. I am pleased to see that a new, efficacious and safe treatment option is now available for these patients.”

The PERSIST-2 study, which assessed the use of pacritinib compared with best available therapy in patients with myelofibrosis and thrombocytopenia, enrolled 311 patients. Those who enrolled were randomized into 1 of 3 treatment regimens, including pacritinib once daily (n = 104), pacritinib twice daily (n = 107), or a best alternative treatment (n = 100). Best alternative treatments included ruxolitinib (45%), hydroxyurea (19%), and prednisone and/or prednisolone (13%).

At the 24-week mark, 15% of patients taking pacritinib once daily and 22% taking the agent twice daily experienced a 35% or higher reduction in spleen volume compared with 3% of those taking a best alternative treatment. Differences between the 3 treatment groups did not reach significance in terms of overall survival, including between the once daily (HR, 1.18; 95% CI, 0.57-2.44) and twice daily pacritinib arms (HR, 0.68; 95% CI, 0.30-1.53). The treatment also yielded a 25% reduction in total symptom score of 50% or more in the pacritinib arms vs 14% in the control group.

Additionally, the phase 3 PERSIST-1 study (NCT01773187) examined the use of pacritinib vs best available therapy for myelofibrosis regardless of baseline cytopenias. Results from the trial indicated that pacritinib was well tolerated and resulted in sustained spleen volume and symptom reduction.3 This study showed that patients with baseline cytopenias could have a treatment option with pacritinib. At week 34, 19% (n = 42) of patients treated with pacritinib experienced a 35% or more reduction in spleen volume reduction compared with 5% (n = 5) in the best alternative treatment group (P = .0003).

The most common grade 3/4 adverse events through week 24 in the pacritinib group were anemia (17%), thrombocytopenia (12%), and diarrhea (5%) compared with anemia (15%), thrombocytopenia (11%), dyspnea (3%), and hypotension (3%) in the best available therapy cohort. A total of 12% (n = 27) of patients died in the pacritinib group and 13% (n = 14) in the best alternative treatment group died.

Pacritinib was also assessed as part of the dose-finding phase 2 PAC203 study (NCT03165734) vs ruxolitinib in patients with myelofibrosis and severe thrombocytopenia.4 Patients who were administered 200 mg of pacritinib twice daily experienced the highest reduction in spleen volume and total symptom score. In particular, patients with a baseline platelet count of less than 50 × 109/L experienced a promising reduction in splenic volume (14%).

Patients who were treated with 200 mg of pacritinib twice a day did not experience an excess of grade 3 or higher hemorrhagic or cardiac events.


  1. CTI BioPharma announces FDA accelerated approval of VONJO™ (pacritinib) for the treatment of adult patients with myelofibrosis and thrombocytopenia. News release. CTI BioPharma Corp. February 28, 2022. Accessed February 28, 2022.
  2. Mascarenhas J, Hoffman R, Talpaz M, et al. Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis. JAMA Oncol. 2018;4(5):652-659. doi:10.1001/jamaoncol.2017.5818
  3. Mesa RA, Vannucchi AM, Mead A, et al. Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial. Lancet Haematol. 2017;4(5):e225-e236. doi:10.1016/S2352-3026(17)30027-3
  4. Gerds AT, Savona MR, Scott BL, et al. Determining the recommended dose of pacritinib: results from the PAC203 dose-finding trial in advanced myelofibrosis. Blood Adv. 2020;4(22):5825-5835. doi:10.1182/bloodadvances.2020003314
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