Pankit Vachhani, MD: If we look at 2 of the most commonly used treatment guidelines, those being the European LeukemiaNet 2018 guidelines for the management of MPNs [myeloproliferative neoplasms], and all of the NCCN [National Comprehensive Cancer Network] guidelines for management of MPNs, I think both have overlap there. Both of these state that there is really no evidence to support the value of disease-modifying therapy in most patients with low or intermediate-1 risk disease. Now, some of these patients may have some requirement for palliative therapies for anemia or splenomegaly, or constitutional symptoms, but for the large part, low or intermediate-1 risk patients don’t need a JAK1 or JAK2 inhibitor. The exceptions being patients who have symptoms or have other indications as I just mentioned. There, observation alone could be performed. Or for example, if someone with low or intermediate-1 risk myelofibrosis has anemia, where that’s the predominant feature, one could target their therapy toward anemia, as long as the other constitutional symptoms or splenomegaly were not the driving factors.

In terms of the cytoreductive therapy, that could be delivered to patients with low or intermediate-1 risk myelofibrosis. The first-line drug that is still being used is hydroxyurea. However, my point will once again stand true that one must carefully look for symptoms in these patients. Should they happen to have symptoms, especially the constitutional symptoms or the vascular symptoms, and also spleen-related symptoms for that matter, one may in those selected cases want to target using JAK1/JAK2 inhibitor therapy. The NCCN guidelines also state it very similarly, and they also emphasize the importance of karyotypic analysis as well as genetic analysis toward the decision-making, even for patients who have what would otherwise be classified as low risk or intermediate-1 risk myelofibrosis.

Now, that having been said, items like yoga or mindfulness exercises have been demonstrated to play a role as nonpharmacologic management approaches. Thus, symptom assessment is key even for patients with low and intermediate-1 risk myelofibrosis. And as previously mentioned, should one have anemia, anemia-directed therapies could be the primary treatment for some of these patients. The corollary of this is that while we are observing our patients and carefully monitoring their symptoms, should one develop progressive splenomegaly or splenomegaly-related symptoms, or for example, if one was to develop new night sweats, weight loss, or any sign or symptom of a loss of response, that could also include, for example, a progressive cytosis, then in those scenarios, one may want to initiate treatment with a JAK1/JAK2 inhibitor early.

Transcript edited for clarity.