Severe ruxolitinib discontinuation syndrome (RDS) was rare in a cohort of patients with myelofibrosis, but even mild RDS was associated with increased spleen size, according to results of a study presented at the Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress.

“Ruxolitinib is a JAK1/2 inhibitor that is approved for the treatment of splenomegaly and symptoms of myelofibrosis,” Francesca Palandri, MD, PhD, of Sant’Orsola-Malpighi University Hospital in Italy, and lead author and presenter, said.

However, a subset of patients who discontinue ruxolitinib experience RDS, which encompasses a variety of AEs that are likely due to rebound cytokine storm. The purpose of this study was to evaluate RDS in a real-world cohort of patients with myelofibrosis.

The multicenter study included 251 patients with myelofibrosis who discontinued their ruxolitinib treatment and survived 30 days or longer thereafter. RDS was defined as any new symptoms that occurred within 21 days after ruxolitinib was discontinued that the treating hematologist deemed related to treatment.


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At the time of ruxolitinib discontinuation, 53% of patients were older than 70 years, 60.6% of patients were male, and 39.8% had primary myelofibrosis.

Ruxolitinib discontinuation occurred as a result of treatment failure in 60% of patients, AEs in 28.6%, and other causes in 10.8%. The ruxolitinib dose ranged from 5 to 20 mg twice daily at the time of discontinuation, but almost 50% of patients used less than 10 mg.

In 35.5% of patients, various approaches such as ruxolitinib taper, taper with prednisone with or without hydroxyurea, or prednisone with or without hydroxyurea, were used in attempt to mitigate RDS.

RDS occurred in 13.5% of patients within 21 days of ruxolitinib discontinuation, with a median time to RDS of 7 days (range, 2-21 days). Severe RDS was rare and occurred in 1.2% of patients.

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Of the patients who developed RDS, 61.8% experienced mild symptoms, which included symptomatic increase in spleen size in 62% of patients; fatigue, itching, bone pain, or abdominal discomfort in 29% of patients; and onset of night sweats, fever, or weight loss in 9%.

An increased risk of developing RDS was significantly associated with platelet count higher than 100 x 109/L (hazard ratio [HR], 2.98; 95% CI, 1.29-6.90; P =.01) and spleen length 10 cm or higher (HR, 2.03; 95% CI, 1.01-4.17; P =.04). Dr Palandri said that this may be because “both factors reflect advanced disease.”

“From this study, we can conclude that severe RDS seems to be a rare event,” Dr Palandri said. “However, its diagnosis is critical because ruxolitinib rechallenge may rapidly improve clinical status.”

Dr Palandri also noted that RDS appears to be associated with large splenomegaly upon ruxolitinib discontinuation.

Reference

Palandri F, Palumbo GA, Elli EM, et al. Ruxolitinib discontinuation syndrome: incidence, risk factors and management in 242 patients with myelofibrosis. Paper Presented at: Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress; June 2020. Abstract S217.

This article originally appeared on Cancer Therapy Advisor