Dr. Verstovsek on Toxicity Profile of Ruxolitinib in MPNs

Srdan Verstovsek, MD, PhD, director of the Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms at The University of Texas MD Anderson Cancer Center, discusses the toxicity profile of ruxolitinib (Jakafi) in the treatment of patients with myeloproliferative neoplasms (MPNs).

One of the biggest challenges with ruxolitinib is the safety of the drug, Verstovsek says. In patients with myelofibrosis, exposure to the drug in clinical trials is 3 years; however, in clinical practice it may not be that long. Researchers have identified some adverse events (AEs) that are of concern, among these events is immunosuppression. As a result, viral infections can be an issue, particularly hepatic infections, which are seen in 5% to 6% of patients. There are other forms of infection like fungal infections that do not appear in clinical trial data, but Verstovsek notes that oncologists should still be cognizant of of them.

In patients with polycythemia vera, a subset of MPNs, they have a slightly better immune system. While there is not the same evidence of infection with ruxolitinib, researchers’ experience with these patients is not as extensive. There was recent literature suggesting an increased risk of lymphoma while being treated with ruxolitinib, but Verstovsek suggests this may be associated with myelofibrosis being a more aggressive disease in general.

In addition, there have been incidences of squamous cell carcinoma, a nonmelanoma skin cancer, developing in these patients. These patients are treated with frontline hydroxyurea, which is well-known to cause these skin issues; second-line ruxolitinib can make it worse.