How the PERSIST-2 Results Show The Benefit of Pacritinib in MF

Targeted Oncology: What was the make-up of the PERSIST-2 trial (NCT02055781) looking at pacritinib (Vonjo) in patients with myelofibrosis (MF)?

JOHN MASCARENHAS, MD: This was the more interesting of the 2 PERSIST studies. PERSIST-2 looked at patients with platelets of 100,000/µL or less.¹ So, the cytopenic patient with MF could have been given a Janus kinase [JAK] inhibitor before being enrolled, and half did in this study...but these are patients that were hard to treat, which was opposite to the set-up of the COMFORT-1 [NCT00952289] and COMFORT-2 [NCT00934544] studies.² [Patients in PERSIST-2 study] were given either 400 mg daily or 200 mg of twice daily pacritinib vs patients on best available therapy [BAT], which could also include ruxolitinib [Jakafi], with a coprimary end point of spleen volume reduction of 35% or more and reduction of the total symptom score at week 24.¹

What stood out among patients enrolled in either arm of the study?

I think what's important to appreciate is when asking the investigator what they would give to patients who were randomly assigned to the BAT arm is that there is a lack of options available. In the BAT arm, 45% of patients got low-dose ruxolitinib, 19% had no options, while some patients were getting hydroxyurea [19%], steroids [13%], and even interferons [2%], which I would argue don't work in this setting.¹ These were patients who had higher-risk disease, and half of them had hemoglobin counts less than 10 g/dL, and the median platelet count was somewhere around 50,000/µL [in a majority of patients in both arms].

John Mascarenhas, MD​

Director

Center of Excellence for Blood Cancers and Myeloid Disorders

Professor of Medicine

Icahn School of Medicine at Mount Sinai​

New York, N

Y

What were the results from this study?

For the patients who got 200 mg of pacritinib twice daily, and that is the approved dose,³ 18% had a spleen volume reduction of 35% or more vs 3% from the BAT arm.1 If you drill down to the patients with less than 50,000/µL platelets specifically, which is what the FDA said is the unmet need here, 29% of [these patients on pacritinib] had a spleen volume reduction of 35% or greater vs 3.1% in the BAT arm, which included those patients on low-dose ruxolitinib.

Symptoms were also improved.... Fifty-percent on the total symptom score is considered the regulatory benchmark for symptom improvement and that was met in 32% [of patients given pacritinib] vs 14% in the BAT arm.¹ There wasn't 1 specific symptom that was driving benefit; no matter which symptom, it was improved to a greater degree with pacritinib being given twice daily. [The improved] symptoms included spleen-related symptoms and clinical cytopenia-related symptoms as well.

Were there any anemia-related outcomes of note?

When we ran the trial, there were anemia responses there that looked different than what we saw with ruxolitinib and fedratinib [Inrebic]. There was a 25% clinical improvement rate with pacritinib, and if we look at red blood cell transfusions at units per month, it was 1.06...at baseline and at week 24 [it was reduced] to 0.67 with pacritinib.¹

We were also seeing these improvements in hemoglobin levels as well as reduction in transfusion burden. There's relative stability in the platelet count with pacritinib. At week 24, there was a dip of about minus 15% to 20%, but that's very different than the minus 40% to 45% that you get with ruxolitinib. You also don't see the same degree of thrombocytopenia, and if anything, over time...you can see in some patients who went from single-digit percentage increases to high double-digit numbers.¹

^References:

^{1. Mascarenhas J, Hoffman R, Talpaz M, et al. Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis: a randomized clinical trial. JAMA Oncol. 2018;4(5):652-659. doi:10.1001/jamaoncol.2017.5818}

^{2. Vannucchi AM, Kantarjian HM, Kiladjian JJ, et al; COMFORT Investigators. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis. Haematologica. 2015;100(9):1139-45. doi:10.3324/haematol.2014.119545}

^{3. FDA approves drug for adults with rare form of bone marrow disorder. FDA. March 1, 2022. Accessed April 19, 2024. https://tinyurl.com/vmwceptu}