Toxicities with Ruxolitinib
In COMFORT-I, the most common adverse reactions observed in patients treated with ruxolitinib included thrombocytopenia, anemia, bruising, dizziness, and headache. Grade 3/4 effects including thrombocytopenia and anemia occurred in 13% (compared with 1% with placebo) and 45% (compared with 19% with placebo) of patients, respectively. Similar results were observed in COMFORT-II.8,9

John Mascarenhas, MD, associate professor of medicine at the Mount Sinai Hospital in New York, New York, described his treatment approach to MF. Based on the Dynamic International Prognostic Scoring System (DIPSS), low-risk patients are observed unless they show disease symptoms. Patients with disease symptoms or intermediate-1 are treated with ruxolitinib and patients with intermediate-2 or higher risk are treated with ruxolitinib and a bone marrow transplant, which Dr Mascarenhas said is the only curative option for MF.

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In reference to anemia and thrombocytopenia seen with ruxolitinib, he asserted there “really is no way around it … Patients must be willing to accept some level of these toxicities if they want to see symptom improvement. If patients have underlying anemia as the main symptom, then ruxolitinib may not be [an] appropriate therapy for them.”

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A recent report in Blood highlighted the increased risk for lymphoma in patients with MPNs who received JAK 1/2 inhibitors.11 In the single-institution study of 626 patients treated for MPNs, 69 received JAK 1/2 inhibitors — and 4 (5.8%) patients developed an aggressive B-cell lymphoma after treatment with JAK 1/2 inhibitors compared with 2 of 557 (0.36%) patients who developed lymphoma on other therapies. The retrospective review concluded that patients receiving JAK 1/2 inhibitors are at a 16-fold increased risk for developing lymphomas.11  

Dr Mascarenhas acknowledged that the risk for developing lymphoma following treatment with ruxolitinib is real. “But another reality is that … secondary malignancies are known to occur in patients with MF regardless of treatment. Even given the small fraction of patients who develop lymphomas, the benefits of therapy outweigh [the] risk,” he said.

Long-Term Follow-Up With Ruxolitinib
A long-term follow-up on overall survival (OS) was provided in an exploratory analysis of the pooled data from COMFORT-I and COMFORT-II.12

Of 528 patients included in the analysis, 301 were originally randomly assigned to receive ruxolitinib and 227 were assigned to receive placebo or BAT. With a hazard ratio (HR) of 0.70, patients on ruxolitinib were at a 30% reduced risk for death (P = .0065). Median OS was 5.3 years for patients on ruxolitinib and 3.8 years for patients on placebo or BAT. When cross over from the placebo/BAT group to ruxolitinib was taken into account, OS was more pronounced: median OS was 5.3 years for patients on ruxolitinib versus 2.3 years for those on placebo/BAT (HR: 0.35; 95% confidence interval: 0.23-0.59). In addition, the analysis showed that the survival benefits were seen regardless of baseline anemia or transfusion needs in patients.12