Ruxolitinib Treatment Reduces Myelofibrosis Symptoms, Spleen Size

Wayne Kuznar

February 2013, Vol 4, No 2 - ASH Annual Meeting


Atlanta, GA—Ruxolitinib (Jakafi) alleviates symptoms such as fever, headache, weight loss, and fatigue, and reduces spleen size in patients with myelofibrosis. This finding, by the French Intergroup of Myeloproliferative Neoplasms (FIM), confirms those from the COMFORT-I and COMFORT-II trials, in which significant reductions in spleen volume were observed with ruxolitinib at weeks 24 and 48.

Ruxolitinib was approved by the US Food and Drug Administration in 2011 for the treatment of intermediate and high-risk myelofibrosis.
This analysis, led by Annalisa Andreoli, MD, Centre d’Investigations Cliniques, Hôpital Saint-Louis, Paris, France, included 241 patients with myelofibrosis, including primary myelofibrosis, postpolycythemia vera, and postessential thrombocythemia.

The patients received ruxolitinib via the Authorization for Temporary Utilization program, a French compassion-based patient initiative. Treat­ment data were gathered at 3-month intervals over 1 year.

Almost all (99.2%) patients were receiving ≥1 therapies for myelofibrosis before taking ruxolitinib. Those therapies included hydroxycarbamide (Hydrea; 90.6%), pipobroman (Vercite 18.4%), immunomodulator drugs (17.1%), interferons (19.2%), erythropoietin (6.9%), splenic irradiation (6.9%), and corticosteroids (4.8%).

“Although the majority of patients were taking other treatments, 93.9% of patients still continued to experience constitutional symptoms, such as fever, malaise, or weight loss; in addition, 94.3% of patients had an evident enlarged spleen [median 15 cm <costal margin] at study start,” Dr Andreoli said.

Treatment with ruxolitinib was started in 132 patients at 15 mg twice daily and in 103 patients at 20 mg twice daily; 6 patients started the drug at other doses.

A mean reduced palpable spleen size was seen in 91.1% of patients at 3 months of treatment and in 83.3% at 6 months.
Constitutional-related symptoms were cleared in 65.3% of patients at 3 months and 70.2% at 6 months. The 21 patients who had 9 months of treatment had a reduction in spleen size and sustained reduced symptoms.

A total of 105 patients had ≥1 adverse event (AE), 33 of whom had severe AEs. The AEs associated with ruxolitinib therapy included hematologic conditions (56.8%), gastrointestinal (5.1%), and cardiac events (2.3%). Hematologic AEs included thrombocytopenia in 60 patients, anemia in 37, and neutropenia in 3 patients.

Overall, 60 patients had dose changes, primarily as a result of thrombocytopenia (n = 36) and anemia (n = 13). In addition, 18 patients stopped treatment (including 7 deaths).