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The novel Janus kinase (JAK) inhibitor ruxolitinib relieves myelofibrosis symptoms, but withdrawal from the drug can be severe, researchers warned.

Serious adverse events requiring hospitalization occurred during drug discontinuation in at least 11% of patients, Ayalew Tefferi, MD, of the Mayo Clinic in Rochester, Minn., and colleagues found.

Withdrawal symptoms included acute relapse of myelofibrosis symptoms, rapid and painful enlargement of the spleen, and acute hemodynamic decompensation, which in some patients led to a septic shock-like syndrome.

This long-term follow-up of 51 Mayo Clinic patients receiving the drug in a larger phase I/II study was reported in a letter published in the Oct. 13 issue of the New England Journal of Medicine.

"It is imperative that patients be alerted about important drug adverse events, including thrombocytopenia, worsening of anemia, and serious withdrawal symptoms," the group urged in the letter.

The incurable bone marrow scarring disease has no FDA-approved treatments. Off-label treatments aim to palliate symptoms from enlargement of the spleen as it attempts to compensate for blood components normally made by the marrow.

Studies with ruxolitinib have shown substantial reductions in spleen size, a reduction in other debilitating symptoms, and improved quality of life as well.

Tefferi's group independently analyzed the long-term outcomes of their patients who got open-label ruxolitinib as part of one of these trials.

Response rates for the individual symptoms among patients experiencing them were:

• 29% for spleen enlargement
• 21% for anemia
• 63% for constitutional symptoms
• 92% for pruritus

Survival rates weren't different than those of a cohort of 410 primary myelofibrosis patients who got standard therapy at the Mayo Clinic over the past decade (P=0.43 or P=0.58 adjusted for risk score).

Side effects were common, including moderate or more severe thrombocytopenia in 26% and anemia in 33%.

About half the patients stopped the drug by one year. Only 11% continued beyond three years.

The largest proportion discontinued ruxolitinib for disease progression or loss or lack of response (40%), followed by toxicity (34%).

Ruxolitinib-maker Incyte filed a new drug application with the FDA in June seeking approval for treatment of myelofibrosis.

The JAK inhibitor was initially developed to tackle myeloproliferative neoplasms and also is being investigated for use in rheumatoid arthritis and psoriasis.

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