Researchers Review Safety Profile of Ruxolitinib in Myelofibrosis

By Cecilia Brown - Last Updated: August 21, 2023

In the years since the US Food and Drug Administration (FDA) approval of ruxolitinib for myelofibrosis, researchers have established its safety profile and shown the “importance of this agent in the [myelofibrosis] armamentarium is clear,” according to a recent review article.

Srdan Verstovsek, MD, PhD, previously of the University of Texas MD Anderson Cancer Center, and colleagues wrote the review article and published it in the Journal of Hematology and Oncology.

Ruxolitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, initially received approval in 2011 from the FDA for patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. The approval was based on efficacy and safety findings from the phase II COMFORT trials.

“Over a decade later, ruxolitinib continues to be the standard of care in higher-risk [myelofibrosis], and dose optimization and management remain crucial for safely maximizing clinical benefits of ruxolitinib,” Dr. Verstovsek and colleagues wrote.

An Overview of Ruxolitinib Data from Clinical Trials, Postmarketing Surveillance

Beyond the COMFORT trials, the safety profile of ruxolitinib was evaluated in the subsequent JUMP, ROBUST, EXPAND, and REALISE trials, as well as pooled analyses and postmarketing analyses, according to the review’s authors.

With ruxolitinib, hematologic adverse events (AEs)—which the review’s authors noted are to “be expected given the mechanism of action as a JAK1/JAK2 inhibitor”—have been “generally manageable” with dose modifications, transfusions, or both. Cytopenias, such as anemia and cytopenia, are the most frequent AEs with ruxolitinib in patients with myelofibrosis, according to the review’s authors.

In terms of nonhematologic AEs, they were “generally observed at a similar rate to placebo or best available therapy in the COMFORT trials.”

The review’s authors additionally provided an overview of the drug’s safety profile outside of clinical trials.

“In general, data from ruxolitinib postmarketing surveillance studies have been consistent with those reported in clinical trials,” they wrote.

They also evaluated the data collected on ruxolitinib in the context of anemia.

“Importantly, presence of anemia is not a contraindication for ruxolitinib use and is not prognostic for response to ruxolitinib treatment,” Dr. Verstovsek and colleagues wrote.

The review also highlighted critical practical considerations for clinicians, with an emphasis on dosing strategies and the impact of the COVID-19 pandemic.

“Of particular note in the COVID-19 era, it is not advisable to discontinue ruxolitinib due to SARS-CoV-2 infection or COVID-19 treatment,” the review’s authors wrote. This recommendation is based on an increased risk of death reported in patients with [myelofibrosis] who discontinued ruxolitinib treatment due to COVID-19 infection.”

They noted that an observational retrospective study showed an 8.5-fold increased risk of death among patients with myelofibrosis and COVID-19 who discontinued ruxolitinib compared with those who continued the therapy.

The review also highlighted tapering strategies, the influence of disease stage and treatment delay on AEs, managing thrombocytopenia, the risk of infections and cardiovascular events, and other key information collected over the years since the approval of ruxolitinib.

“With ruxolitinib remaining the standard of care in [myelofibrosis] more than a decade after its initial approval, the importance of this agent in the [myelofibrosis] armamentarium is clear,” Dr. Verstovsek and colleagues concluded. Future analyses may shed further light on the ruxolitinib safety profile, including dose optimization strategies for ruxolitinib treatment interruptions or discontinuations and use in combination regimens.”


Verstovsek S, Mesa RA, Livingston RA, Hu W, Mascarenhas J. Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety. J Hematol Oncol. 2023;16(1). doi:10.1186/s13045-023-01471-z

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