Evaluating PRM-151 in Patients With Myelofibrosis Resistant or Intolerant to Ruxolitinib

According to results from a double-blind, phase II study, PRM-151 improved bone marrow fibrosis grade, transfusion dependence, and symptoms in a cohort of patients with higher-risk myelofibrosis who were intolerant of, had an inadequate response to, or were ineligible to receive ruxolitinib, the only approved therapy for myelofibrosis.

The results were presented by Srdan Verstovsek, MD, PhD, from The University of Texas MD Anderson Cancer Center in Houston, at the 24th Congress of the European Hematology Association.

PRM-151, a recombinant human pentraxin-2 molecule, has been shown to prevent and reverse fibrosis in animal models of myelofibrosis by targeting differentiation of fibrocytes from monocytes.

In the first stage of this trial the agent, when given in combination with ruxolitinib, decreased patients’ bone marrow fibrosis and improved hemoglobin and platelet levels.
Dr. Verstovsek reported results from the second stage of the trial, which evaluated efficacy and safety of three doses of PRM-151 as a single agent in 97 patients. Participants had intermediate-1, intermediate-2, or high-risk primary myelofibrosis or post–essential thrombocythemia/polycythemia vera myelofibrosis.

Patients were stratified according to baseline hemoglobin (Hb) levels and transfusion dependence, then randomized to receive PRM-151 at one of three assigned doses:

  • 0.3 mg/kg (n=33)
  • 3 mg/kg (n=32)
  • 10 mg/kg (n=32)

The agent was administered intravenously on days 1, 3, and 5 of cycle 1 and on day 1 of each subsequent 28-day cycle. Treatment continued for at least nine cycles.

“The study enrolled a large proportion of [patients with myelofibrosis] with advanced disease,” the authors noted. At baseline, most patients (n=61; 64%) had grade 3 bone marrow fibrosis and the most common diagnosis was primary myelofibrosis (n=66; 68%). Similar proportions of patients across the dosing groups were anemic or transfusion dependent (TABLE).

The investigators obtained bone marrow biopsies and imaging for spleen volume at baseline, cycle 4, cycle 7, and cycle 9 to measure reductions in bone marrow fibrosis grade (primary objective).

At the time of data cutoff, 46 patients discontinued treatment prior to starting the ninth cycle of PRM-151.

According to review by independent pathologists, decrease in bone marrow fibrosis score (by ≥1 during any timepoint) was observed across all dose levels:

  • 10 of 33 patients (30%) at 0.3 mg/kg
  • 9 of 31 patients (28%) at 3 mg/kg
  • 8 of 32 patients (25%) at 10 mg/kg

The investigators also observed reductions in transfusion dependence in patients who required red blood cell transfusions at baseline or who had Hb lower than 100 g/L: 16% to 29% of patients experienced a 50% or greater reduction in red blood cell transfusions or Hb increases of 10 g/L or higher for longer than 12 consecutive weeks.

The same relationship was observed in patients who were platelet transfusion–dependent or had platelets between 25 and 50×109/L, the authors reported. Thirty-one to 40% of these patients had a >50% reduction in platelet transfusions or a doubling of their platelet count or remained transfusion-independent for longer than 12 consecutive weeks.

In addition, approximately 10% to 26% of patients experienced a >25% reduction in their baseline Total Symptom Score for longer than 12 consecutive weeks.

“Response rates … were generally similar across the three dose levels,” the researchers stated. The most common treatment-emergent adverse events (AEs) were fatigue, cough, thrombocytopenia, and abnormal weight loss. Most of these were grade 2 or lower, but grade 3 and 4 AEs were reported in 12% and 6% of patients, respectively.

The investigators concluded that these data warrant confirmation in a larger controlled study, as the findings are limited by the lack of a comparator group.

The authors report relationships with Promedior, which sponsored the study.


Verstovsek S, Talpaz M, Wadleigh M, et al. A randomized, double blind phase 2 study of 3 different doses of PRM-151 in patients with myelofibrosis who were previously treated with or ineligible for ruxolitinib. Abstract #S828. Presented at the 24th European Hematology Association Annual Congress, June 15, 2019; Amsterdam, The Netherlands.