The last decade has seen tremendous advances in the myeloproliferative neoplasms (MPNs), polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF). Genetic profiling demonstrated that all patients with MPNs have activated JAK2 signaling.

The FDA approval of ruxolitinib, a JAK2 inhibitor, for the treatment of intermediate and high-risk MF and for patients with polycythemia vera who cannot tolerate or inadequately respond to hydroxyurea has transformed care for this challenging group of diseases, according to a recent review article in Blood.

Oral agents. Source

“The introduction of JAKis in clinical practice has raised the bar of treatment goals in MF and PV,” Francesco Passamonti, MD, Head of the Division of Hematology of the University Hospital of Varese, in Italy, and colleagues wrote.

In clinical practice, ruxolitinib has achieved a 50% spleen volume reduction in about 60% of patients with advanced myelofibrosis with a median duration of response of 3.2 years and an associated reduction in the risk of death. That level of reduction has set current expectation, “meaning that new drugs or combinations must overcome this result,” the researchers added.

In addition, ruxolitinib reverses cytokines and associated inflammation, complications and survival. Patients also experience significant symptom reduction and, based on the COMFORT trials, longer survival, with a median survival of 5.3 years.

Less than 5% of MPN patients have primary resistance to JAK inhibitors, but some do lose spleen response over time. Consequently, the authors recommend using the highest safe dose to maximize benefit. Patients may also develop resistance to JAK inhibitors and those patients should be considered for clinical trials.

Based on the COMFORT studies, any MF patient can benefit from ruxolitinib, the authors said, but those with three or more mutations had less spleen response and short time to treatment discontinuation. Patients in higher risk categories and those who delay the start of ruxolitinib also have lower rates of response, which they noted, argues for initiating ruxolitinib earlier in the disease course, as recommended by the National Cooperative Cancer Network guidelines. Those guidelines call for using ruxolitinib in low and intermediate-1 risk MF patients with troublesome symptoms and recent studies indicate greater than 60% efficacy and a good safety profile for use in these patients.