Treatment Option for Patients with Myelofibrosis and Lower Platelet Counts

RDR Staff

Currently, there is a treatment for patients with intermediate- or high-risk myelofibrosis. They can be prescribed ruxolitinib, and dosing is linked to platelet counts starting at 50,000/μL (50 x 109/L to <100 x 109/L).1 But what about patients with platelet counts below 50,000/uL?
According to Ruben A. Mesa, MD, director of the Mayo Clinic Cancer Center in Scottsdale, Arizona, 25% of patients with myelofibrosis have platelet levels below that threshold at the time of diagnosis, and the incidence rises to the 30%-to-50% range as patients undergo therapy. “As early as 1 year from the time of diagnosis, the incidence of disease-related thrombocytopenia, anemia, and red blood cell transfusion requirements increases dramatically,” said Dr. Mesa said in his presentation at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.2

“At this point, under 50,000 there are no approved therapies,” said Dr. Mesa. “There will be off-label use of therapies, even off-label use of ruxolitinib,” but at lower dose levels that might impair its efficacy.

Fortunately, a new study, with a new JAK2 inhibitor, pacritinib, may benefit all patients with myelofibrosis, including those below the 50,000-platelet threshold.
At ASCO 2015, data from the PERSIST trial2 were presented that involved 327 patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis were eligible to enroll. There was no required platelet level for enrollment; 32% had platelet levels <100,000/μL and 15% had counts <50,000/μL.

In the PERSIST-1 trial, patients were randomized 2:1 to receive pacritinib 400 mg daily versus physician’s choice of best available therapy (BAT), excluding prior ruxolitinib. Hydroxycarbamide (55.7%) and a watch-and-wait strategy (25.5%) were the most prevalent approaches in the control arm.

Patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis were eligible to enroll. There was no required platelet level for enrollment; 32% had platelet levels <100,000/μL and 15% had counts <50,000/μL.
Pacritinib demonstrated superior outcomes in every measure. The primary endpoint of spleen volume reduction (SVR) ≥35% was achieved not only in the intent-to-treat (ITT) population, but also among evaluable patients. (The ITT population consisted of 220 patients who received pacritinib and 107 who were given BAT).
Among evaluable patients, 25% of participants who received pacritinib (n = 168) reached the SVR threshold versus 5.9% in the BAT arm (n = 85; P =.0001).

The differences were even more pronounced for patients with baseline thrombocytopenia. Among this group, the percentages of patients with <50,000/μL platelets who achieved SVR ≥35% were 22.9% and 33.3% for the ITT and evaluable populations, respectively. For those patients with baseline thrombocytopenia and <100,000/μL platelets, 16.7% and 23.5% achieved SVR ≥35% in the ITT and evaluable groups, respectively.

Notably, the rates of SVR correlated with overall survival, with patients who received pacritinib experiencing greater benefits, Dr. Mesa indicated. Among patients who were dependent upon red blood cell transfusions, 25.7% of those who received pacritinib became independent during the trial, whereas none of those on BAT reached this milestone (P =.043), according to the conference abstract.

The abstract also reported that the most common adverse events (AEs) for pacritinib were diarrhea, nausea, and vomiting, with a low incidence of grade 3 AEs.2

Conclusions and Next Steps

“Based on preliminary data, pacritinib may be disease-modifying and warrants combination studies with other potentially disease-modifying agents in myeloproliferative neoplasms,” Dr. Mesa said.
“The goal is to have an impact on the disease by reducing splenomegaly and symptoms,” Dr. Mesa said. “We believe that as a class, the JAK inhibitors likely have an impact upon survival, probably by decreasing the morbidity of the disease. Many patients with myelofibrosis really die of complications related to the disease such as pneumonia or heart failure—they develop thrombosis. That debilitation, when it’s reversed, we think is impactful in terms of their outcomes.”

Research into pacritinib is continuing with the phase 3 PERSIST-2 trial, which is evaluating the drug in comparison with BAT that may include ruxolitinib among patients with myelofibrosis with platelet counts ≤100,000/μL, according to CTI BioPharma, the Seattle-based company developing the agent.3

About Myelofibrosis

Myelofibrosis is 1 of 3 main types of myeloproliferative neoplasms.  The other 2 types are polycythemia vera and essential thrombocytopenia. Myelofibrosis is a serious and life-threatening chronic bone marrow disorder caused by the accumulation of malignant bone marrow cells that triggers an inflammatory response and scars the bone marrow. The replacement of bone marrow with scar tissue limits its ability to produce red blood cells, prompting the spleen and liver to take over this function.

Approximately 18,000 people in the United States have myelofibrosis. US median survival for patients with myelofibrosis is approximately 6 years.  Currently, Jakafi (ruxolitinib) is the only approved orphan drug for these patients.


  1. Jakafi [prescribing information]. Wilmington, DE: Incyte Corporation; 2014.
  2. Mesa RA, Egyed M, Szoke A, et al. Results of the PERSIST-1 phase III study of pacritinib (PAC) versus best available therapy (BAT) in primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia myelofibrosis (PET-MF).  Presented at: the 2015 American Society of Clinical Oncology Annual Meeting; May 29-June 2, 2015; Chicago, IL. Abstract LBA7006.
  3. PERSIST 2. CTI BioPhama Corporation website. Accessed May 30, 2015.
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