JAK Inhibitors and Resistance in Myelofibrosis


Anthony Hunter, MD, discusses JAK inhibitor resistance and optimal strategies for treatment of patients with myelofibrosis.

Anthony Hunter, MD, assistant professor, Department of Hematology and Medical Oncology Emory University School of Medicine, medical director, Immediate Care Center, Winship Cancer Institute of Emory University, discusses JAK inhibitor resistance and optimal strategies for treatment of patients with myelofibrosis.


0:09 | JAK inhibitor resistance has been defined a little bit differently in different studies. Overall, failure includes sort of intolerance to treatment, and then that resistance/refractory sort of category can include patients who really never responded appropriately to agents, or who initially did have some response like spleen reductions, but then that spleen started to grow back instead of losing that response.

0:32 | What we know is that these patients historically do poorly. The full mechanisms this are not necessarily fully understood, and we do see that although this JAK/STAT pathway is sort of the key player in pathogenesis of myelofibrosis, there are many other signaling pathways. [There is] the PI3 kinase pathway, the RAS/MAPK pathway, and multiple of these other signaling pathways that are activated in myelofibrosis and likely lead, to the rationale that we can't sort of cure the disease, obviously, with JAK inhibitors. [There is] still more to learn about you the exact sort of mechanisms for all this.

1:04 | We do now know that with multiple JAK inhibitors, historically after ruxolitinib [Rituxan] failure patients have done very poorly [with] survival [at] a little bit over a year. [There is a] lack of good treatment options, historically, but with sort of multiple emerging JAK inhibitors now either already approved or sort of likely to come out soon, many of which have data sort of in that second-line ruxolitinib failure setting, we're gonna have more ability now to sort of salvage some of these patients with another JAK inhibitor, as well as a number of clinical trials, [including] with non JAK inhibitor therapy either alone or in combination with the JAK inhibitor that are emerging [and] that will be important for this population.

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