Discontinuation of Jakafi May Result in Poorer Survival in Myelofibrosis Treatment

Survival among patients with myelofibrosis who discontinued treatment with Jakafi (ruxolitinib) appeared to have poorer survival, according to study results published in JAMA Oncology.

This was seen particularly in those who discontinued treatment during the blast phase — the body's rapid attempt to restore homeostasis after tissue injury, infection, neoplastic growth, or immunological disturbance.

“Ruxolitinib is the first-in-class JAK1/JAK2 inhibitor commercially available for the treatment of (myelofibrosis),” the researcher wrote. “Ruxolitinib ameliorates inflammation and proliferation, which leads to clinically relevant control of splenomegaly (enlargement of the spleen) and symptoms in the majority of patients with (myelofibrosis), which may result in prolonged survival.”

However, some patients are unable to target the drug, and consequently, discontinue treatment.

“The management of patients with (myelofibrosis) after ruxolitinib represents a major challenge in real-life clinical practice,” the researchers added.

In this study, they evaluated 218 patients after treatment with Jakafi to determine whether disease characteristics before the receipt of Jakafi may predict drug discontinuation in patients with myelofibrosis and whether reasons for drug discontinuation, disease phase at discontinuation and salvage therapies may influence this outcome.

At three years, 40.8% of patients had stopped treatment with Jakafi. At last contact, 268 patients (51.1%) had discontinued therapy, and the median drug exposure was 17.5 months.

In total, 50 patients (18.7%) died while taking Jakafi. The reasons for discontinuation in the remaining 218 patients were the lack (22.9%) or loss (11.9%) of a spleen response, Jakafi-related side effects (27.5%), progression to blast phase (23.4%), Jakafi-unrelated side effects (9.2%), and allogeneic transplantation during response (5.1%).

“First, failure to achieve or maintain a significant spleen response was the main cause of discontinuation, probably because ruxolitinib is initiated in most patients to target this specific clinical need,” the researchers explained. “Second, almost 20% of patients discontinued because of hematologic toxicity… Third, the current study points out that infections may lead to discontinuation in a substantial fraction of ruxolitinib-treated patients, reinforcing the recommendation for close infectious monitoring before and during therapy.”

Median survival after treatment with Jakafi was 13.2 months, which was significantly improved in the 167 patients who discontinued treatment during the chronic phase (treatment to restore blood counts to normal levels compared with those who discontinued in blast phase (27.5 months versus 2.9 months, respectively).

The researchers did not observe any survival differences among patients who discontinued Jakafi in the chronic phase because of a lack of response, loss of response, or Jakafi-related side effects. “These observations may indicate that ruxolitinib-induced toxicity is not predictive of inferior survival.” The researchers wrote.

The use of investigational agents and/or Jakafi rechallenge (to try a therapeutic agent on a patient a second or subsequent time to see if the suspected effects of the treatment occur again) were associated with improved outcome.

“Salvage therapies can improve outcome, emphasizing the need for novel therapies,” the researchers wrote.