Evidence-Based Use of JAK Inhibitors in Myelofibrosis
In this expert Q&A, Junaid Anwar, MD, a hematology-oncology fellow at UT Health Houston, reviews the current evidence base for Janus kinase (JAK) inhibitors in myelofibrosis derived from a pooled analysis of five phase 3 trials. He explains why ruxolitinib remains the standard of care for symptom relief and spleen reduction, outlines scenarios in which fedratinib and pacritinib may offer advantages, and clarifies where momelotinib fits—particularly for anemia—while emphasizing the need for ongoing research into combination strategies and emerging agents. Dr Anwar presented these findings at the 2025 SOHO Annual Meeting in Houston, TX.
Additional Resource:
- Anwar J, Ijaz H, Saif P, Devi S, et al. JAK inhibitors vs best available therapy for myelofibrosis: a meta-analysis of randomized clinical trials. Presented at: Society of Hematologic Oncology (SOHO) Annual Meeting; September 3–6, 2025; Houston, TX. https://www.sohoonline.org/SOHO2025/SOHO2025/Home.aspx?hkey=93a9c2f1-f560-44a0-85d3-9ef0b19cdab8
Junaid Anwar, MD: My name is Junaid Anwar. I'm a hematology oncology fellow at UT Health Houston. And currently I'm doing my first year of fellowship here, and my interest is in, like, hematologic malignancies.
Consultant360: What do you feel are the most important takeaways from your meta-analysis?
Dr Anwar: So basically, it's a general meta-analysis on myelofibrosis and the current treatments that are available, especially JAK inhibitors. So, we did a meta-analysis on five landmark trials. They are on JAK inhibitors. So, JAK inhibitors are the main line of management. It's basically one type of therapy to improve quality of life in patients with myelofibrosis. Myelofibrosis is a disease that is very debilitating. It has debilitating symptoms, and so our aim, our target in this disease is to improve patients' quality of life.
This disease has patients present with a big spleen. So, our target, these therapies, they target two main areas. One is to decrease the size of the spleen, and the other is to improve symptoms. So, these are the key endpoints which all of these trials also target.
And, so what I concluded, the key takeaway is these therapies, JAK inhibitors, that include ruxolitinib, fedratinib, pacritinib, and all of these therapies, when they are compared with the best available therapy at their time in the trial, they had better outcomes when it comes to symptoms, and when it comes to reducing the spleen size. So that's just a general takeaway from my meta-analysis.
C360: Why do you feel this research is especially relevant for clinicians and researchers right now?
Dr Anwar: Yeah, so, like I said, you know, this is the standard of care. To start the treatment with ruxolitinib, which is the first line JAK inhibitor therapy that is given to all the patients with myelofibrosis. And, so my meta-analysis, this is a concise meta-analysis that just combines the results of all five landmark trials.
There was not a meta-analysis that was done before that combined all these five different trials together. So this is the first meta-analysis to just increase the effect size, you know, so increase your population, and then increase the effect size, and see what the effect of these JAK inhibitors is when the population size is bigger.
So that's what we tried to calculate, and so the key takeaway for clinicians—whatever the data is available at this point for clinicians, it reinforced that. We basically came up with results that are similar to what the standard of care is right now. But we added a few more points, which are specific to all different kinds of JAK inhibitors; like today, the standard of care is to start with ruxolitinib, which is the first line. So, our meta-analysis also concluded that ruxolitinib has a better efficacy compared to others. And side effect profile is better with ruxolitinib.
When some people are intolerant to ruxolitinib, or they are refractory to ruxolitinib, the fedratinib becomes the better next choice. So, that's what we tried to see in our meta-analysis, that the fedratinib was a better option when people become refractory to ruxolitinib. Another point that we noticed in our meta-analysis was, if someone is on ruxolitinib, which is a first-line treatment, and they have a big spleen, it's not useful to switch to momelotinib, because the systematic review showed that the trial that was done on momelotinib, it did not show any superiority over ruxolitinib when it came to spleen size, but it was superior when we just had to manage anemia symptoms.
Similarly, pacritinib. So, the two trials that we included on pacritinib, they concluded that patients who had myelofibrosis, but also had thrombocytopenia, with platelet count less than 100,000—those patients benefited more with pacritinib compared to standard of care, and that also included ruxolitinib. So basically, these trials, they compared pacritinib versus ruxolitinib, and ruxolitinib, like I said, is our standard of care. But these trials concluded that pacritinib is better than ruxolitinib in patients where the platelet count is less than 100,000.
So, yeah, that is another thing that we came up with. It was already a kind of practice to go that way, but our meta-analysis just came up with evidence that, yeah, this definitely is better than ruxolitinib in that population.
C360: So, how should clinicians balance the higher efficacy of JAK inhibitors with the increased risk of adverse events?
Dr Anwar: Yeah, that's a good point. So, what we observed in our meta-analysis was ruxolitinib, like I said, has a better side effect profile compared to other JAK inhibitors, and efficacy is better. So that's why it's the standard of care, right? Because we try to minimize side effects. But when you go towards a newer JAK inhibitor, like pacritinib, like I described, the side effects are increasing, there is increased frequency of having these side effects, like grade 3 anemia. thrombocytopenia and GI side effects with pacritinib.
The current standard practice is to start with ruxolitinib, which is an optimal way to, go, because its side effect profile is less. But when you go to fedratinib, pacritinib, and momelotinib, the side effect profile is compromising.
C360: What key gaps in knowledge or unanswered questions do you feel remain when it comes to treating patients with myelofibrosis?
Dr Anwar: As a clinician, we try to manage symptoms in myelofibrosis, and we try to reduce the size of the spleen. All of these help improve quality of life.So that's what we are aiming for with this therapy. And I would say the future of myelofibrosis goes towards the newer agents that are being studied and investigated, like these telomerase inhibitors, these therapies, they basically try to cure the disease and come up with a remission. So, I think the future lies towards utilizing a combination of JAK inhibitors and these newer therapies, like telomerase inhibitors. But there are no phase 3 trials that have concluded on these therapies, and I believe there is a gap that needs to be fulfilled.