Gaining More Benefit from Ruxolitinib for Patients With Polycythemia Vera, Other MPNs

Special ReportsHematologic Malignancies: Polycythemia Vera
Volume 3
Issue 3

Since its approval 5 years ago, ruxolitinib (Jakafi) continues to drastically change the treatment landscape and quality of life of patients with myeloproliferative neoplasms (MPNs), including a subset of patients with the bone marrow neoplasm, polycythemia vera (PV).

Kiran Naqvi, MD

Since its approval 5 years ago, ruxolitinib (Jakafi) continues to drastically change the treatment landscape and quality of life of patients with myeloproliferative neoplasms (MPNs), including a subset of patients with the bone marrow neoplasm, polycythemia vera (PV).

The FDA approved ruxolitinib in PV only for patients who are intolerant of or resistant to the cytoreductive agent hydroxurea, but Kiran Naqvi, MD, assistant professor of Leukemia at the University of Texas MD Anderson Cancer Center, predicts that the drug will be explored in combinations for not only the treatment of PV, but for MPNs in general.

“We see people who have PV progress to myelofibrosis then to aggressive myelofibrosis,” Naqvi said in an interview withTargeted Oncology. “If somebody has already been on ruxolitinib for PV [and progresses], then I think at that point we have to start thinking about a combination treatment to help the disease from progressing.”

Naqvi mentioned upcoming and current trials that are combining ruxolitinib with azacytadine or decitabine to improve outcomes of the patients who have progressed and possibly expand the use of the drug to more people. Right now, Naqvi said she does not treat patients with PV who are younger than 60 years in age or who have no history of blood clots.

The majority of patients with PV have a JAK2 mutation, and with ruxolitinib acting as both a JAK1 and JAK2 pathway inhibitor, the drug quickly acts to improve quality of life by reducing symptoms such as splenomegaly, fatigue, fever, and weight loss.

Though about 90% of patients see a full response on hydroxyurea, according to a recent review published inCritical Reviews in Oncology Hematology, about 24% of patients eventually develop an intolerance or resistance.1Criteria for resistance, according to the study, was the need for phlebotomies, platelet or white blood cell count increase to certain levels, failure to reduce spleen size by 50% or more, or the failure to reduce the spleen at all after 3 or more months at the maximum-tolerated dose.

Before the approval of ruxolitinib, these patients had few other alternatives, thus facing severe side effects ranging from nausea and fatigue to myelosuppression, where bone marrow activity is decreased. They were also at a higher risk of death, transformation to myelofibrosis, or acute myeloid leukemia (AML).

The review, led by Aziz Nazha, MD, department of Hematology and Medical Oncology at the Cleveland Clinic, noted, “In 2 randomized clinical trials comparing ruxolitinib to either placebo or best available therapy in patients with primary myelofibrosis, patients who received ruxolitinib had significant reduction in their splenomegaly and significant improvement in their constitutional symptoms and quality of life scores.”

Another study, conducted by Naqvi and a team of researchers at MD Anderson, sought out to discover if patients who were treated with ruxolitinib off-trial had the same results as those who were given the drug during clinical trials, such as the COMFORT studies.2

“We confirmed that the patients who were treated with ruxolitinib off-study have the same degree of improvement with regard to spleen size. The spleen shrinks,” Naqvi said. “We also found that even if the patients have been exposed to some kind of JAK inhibitor in the past and then get ruxolitinib as a second-line treatment, they still respond to treatment.”

She did mention, though, that the duration of response was not as durable for those who have previously failed on another JAK inhibitor.

Naqvi’s study included a broader range of MPN types, not just myelofibrosis. A small number of patients with chronic myelomonocytic leukemia (CMML), essential thrombocythemia (ET), and polycythemia vera (PV), though in small numbers, were all included.

Other studies are also looking toward expanding the use of ruxolitinib in patients with PV, such as Novartis’ phase III open-label, single arm, multi-center, expanded treatment protocol study (NCT02292446). The purpose of the study is to measure safety and tolerability of ruxolitinib in patients who are resistant to or intolerant of hydroxyurea and do not have any other standard treatment options, or qualify for another PV-related clinical trial. Currently, the study is recruiting patients from around the world.

While the main mechanism of ruxolitinib is to treat the constitution symptoms such as enlarged spleen size, Naqvi said that clinicians are starting to see a survival benefit after a few years of the drug being approved.

“It’s amazing,” Naqvi said of the drug. “It’s had a great impact [on these patients].”


  1. Nazha A, Khoury JD, Verstovsek S, et al. Second line therapies in polycythemia vera: What is the optimal strategy after hydroxyurea failure?Crit Rev Oncol Hematol.2016;105:112-117.
  2. Naqvi K, Pierce S, Zhou L, et al. Role of ruxolitinib in patients (pts) with myeloproliferative neoplasms (MPNs) treated off clinical trial.J Clin Oncol33, 2015 (suppl; abstr e18076).
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