SOHO 2023 | Clinical guidance for the use of JAK inhibitors when treating patients with MF

JAK inhibitors have been our mainstay in myelofibrosis therapy for about a decade, a little over a decade now, since ruxolitinib was approved. And so, a little bit newer now with multiple agents coming out, but still, a lot of those drugs achieve the same things. And so, many patients do benefit from JAK inhibitor use, but not necessarily all of them. We do see a subset of patients who predominantly have anemia, or patients who are very low-risk disease and don’t have much in the way of symptoms who do not necessarily need a JAK inhibitor, at least in the front-line setting. Contrary to that, in patients who are higher risk and have significant spleen and symptoms, we do see a benefit by using it early in the disease course. It is important to these symptomatic patients and high-risk patients to try and use JAK inhibitors early on. When we’re treating with these agents, generally patients do tend to feel better by shrinking spleens down and improving those symptoms, but certainly you can see some toxicity. A couple of the agents we do see some GI toxicity with- so it’s important to counsel on that and provide supportive care in the first couple of months until that typically does resolve. Also important particularly in patients on ruxolitinib and fedratinib, where we can see quite a drop in hemoglobin and platelet counts, mostly in the first two to three months of therapy where we really see that occur. So it’s important to monitor blood counts very closely in the first couple of months. Generally, once we see those start to plateau, we space out how often we’re seeing those patients again. There is some risk of infections and opportunistic infections, so that is something to keep in mind in patients when we’re using these agents as well, as well as potentially an increased risk of non-melanoma skin cancers that are important to keep an eye on in these patients as well. But generally, once we are using it, especially with agents like ruxolitinib with different doses, it’s important to optimize that dose to try and achieve effective doses and titrate the dosing to response. You do have to be careful about blood counts and things like that, but certainly especially with ruxolitinib, we see a clear dose response effect for spleen and symptom response. It is important to try to get up to those optimal doses and maintain patients on dosing, as long as they’re continuing to get some benefit from the drug. Now, we do have some data with these newer agents of second line JAK inhibitor use as well, which is an important aspect for these. A key thing when you’re thinking about switching or stopping these is that you certainly do not want to abruptly stop JAK inhibitors. You can see a very dramatic withdrawal symptom, and patients can get pretty sick from that. So it is important to, if you’re stopping altogether, to taper that off- generally over a few weeks. Ideally, what you want to do is have a backup option in mind that you’re going to immediately transition them to- often another JAK inhibitor. Now, certainly, clinical trials are an important option in this setting as well. But I generally do continue ruxolitinib with the thought that it’s giving at least some benefit until I’m immediately starting on that next line of therapy to avoid acute worsening of the disease and some of the things that we can see when stopping a JAK inhibitor.