Management of Myelofibrosis and Adverse Events sees Progression With new JAK Inhibitors

September 21, 2019
Conor Killmurray

With the approval of 2 new JAK inhibitors for the management and treatment of myelofibrosis, the space is undergoing a new progression, with lots of questions left to answer.

Management and treatment of myelofibrosis has seen new progression with the approvals of 2 new JAK inhibitors, ruxolitinb (Jakafi) and fedratinib (Inrebic). Each of these drugs were major milestones in the myelofibrosis space, as ruxolitinb was the first and only drug to be approved for patients with steroid-refractory acute graft-versus-host disease (GVHD) and fedratinib was the first drug approved for patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis in almost a decade.

While these approvals have made huge strides for patient outcomes, there still needs to be more research on potential combination strategies and the development of novel agents, according to Laura C. Michaelis, MD, associate professor at the Medical College of Wisconsin. “There are large categories of treatments that are coming down the pipeline and may be able to mitigate some of the toxicities or failure to respond in some of our higher-risk patients,” Michaelis said in an interview with OncLive®, a sister publication of Oncology Nursing News®, at the 2019 Society of Hematologic Oncology (SOHO) Annual Meeting.

Both of these drugs have yet to undergo significant studies that show which groups of patients might benefit more from either drug as many physicians are just starting to figure out how to apply fedratinib for their treatment plans and which patients are the right patients to move forward with it. For Michaelis, she described 2 patients who had inadequate responses who progressed on ruxolitinib and she is now looking at fedratinib as second-line therapy. For patients that experience GVHD, ruxolitinib has the potential to change their treatment entirely but is not the only treatment for them. Most patients experiencing GVHD are treated with immune suppression, sometimes in the form of multiple agents like steroids, but according to Michaelis comes with its own adverse events (AEs), such as fever and infection due to a chronic immune suppression. However, both JAK inhibitors are tolerable drugs for most patients. “We forget, especially when talking to patients, how poor they really feel with advanced myelofibrosis,” she said. “Many patients are willing to tolerate some of these AEs in order to feel better from their underlying disease.”

With this caveat, Michaelis discussed that it’s important for any care team to have serious discussions with their patients to help determine the best options of treatment as she explained, “I go through treatment options and explain that, ‘This one might not cure you, but it might make you feel better. This one could cure you but might make you feel worse.’ We make a debate that way. It's important to identify the patient's individual goals and then apply the toolbox that we have to address those goals.”

This is where further study not only needs to be applied for ruxolitinib and fedratinib, but in the myelofibrosis landscape as well. JAK inhibitors are only a piece of the puzzle in this case as Michaelis discussed that important questions still need to be asked about when patients need drugs to prevent the disease from spreading, or if novel therapies are needed to tackle the disease at different areas of vulnerability and not just in the JAK-STAT pathway.

A version of this article originally appeared on OncLive® as, “Myelofibrosis Management Makes Strides With JAK Inhibitors, But Work Remains