During a Case-Based Roundtable® event, John Mascarenhas, MD, discussed the efficacy data behind the use of pacritinib in patients with myelofibrosis in the first article of a 2-part series.
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].
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
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