Closing out their discussion on myelofibrosis, experts provide practical advice for identifying and managing patients in real-world practice.
Ruben Mesa, MD: It's a very fluid time for patients with myelofibrosis [MF], with many evolving options. We had ruxolitinib as our only approved agent for a very long time, from 2012 through 2019. Everyone is very comfortable with the agent. It's a solid agent, but there are many patients out there that may benefit either from 1 of the new agents, fedratinib or pacritinib, or potentially be eligible or might even benefit from clinical trials. Indeed, several of these clinical trials are up-front clinical trials for individuals that are JAK [Janus kinase] inhibitor naïve. As you have patients with myelofibrosis, it may be worthwhile for you to connect with a friend or colleague that focuses on MF; myself, Dr [Srdan] Verstovsek [MD, PhD, at MD Anderson Cancer Center in Houston, Texas], or anyone in the MPN [myeloproliferative neoplasms] community, just to see, based on that individual patient or circumstance, whether there is a trial. What would be the advantages of considering that? If they are on ruxolitinib having a suboptimal response, there may well be good opportunities for them, both in commercially available drugs, but also with clinical trials. It's evolving. It's a lot to keep track of, so reaching out if you have a new patient or something isn't going as you would like, is helpful.
Stephen T. Oh, MD, PhD: As far as practical pearls and managing treatments with myelofibrosis, I would mention a couple of things. The first is that we know that managing and dealing with cytopenias in patients with myelofibrosis can be difficult. And more specifically, when using drugs such as ruxolitinib in conjunction or consideration of patients with anemia and or thrombocytopenia, this can be a little bit challenging. For instance, if you have a patient with a baseline hemoglobin of 8.5 or 9, and you start the patient on treatment of ruxolitinib, their anemia can get worse. This, in some cases, prompts either the patient or the treating physician to decide to discontinue ruxolitinib, and that may be appropriate. But really, I think my pearl here is that we have to consider the overall benefit to the patient. If a patient is really fatigued and they began treatment with ruxolitinib and their hemoglobin does go down a little bit but they feel better overall—which is often the case—then, I would continue the ruxolitinib even in the face of worsening anemia. That's my first pearl: to not necessarily avoid the use of ruxolitinib even in the setting of anemia. In a good way, this may evolve in the near future with agents such as momelotinib coming to the fore, where there actually won't be so much of an issue, and in fact, anemia may improve. But with the current use of ruxolitinib, that's something that I've seen a number of times, where either the patient or the treating physician or both have elected to discontinue ruxolitinib. If the patient comes to see me, I may say “Actually, you might be better off if we resume the ruxolitinib.”
And the other pearl related to that is in the setting of thrombocytopenia. We know from the available data that in patients who have severe thrombocytopenia, achieving an effective dose of ruxolitinib becomes very difficult. For instance, if a patient's platelets are so low that the only dose they can be given is something like 5 milligrams once a day or 5 milligrams twice a day, the likelihood of achieving a substantial spleen and or symptom response is not all that high. It's not really expected that you will see much benefit with that kind of a low dose. Thus, that is where I think we have now the latitude with the availability of pacritinib to use that agent for those patients where we can dose the drug potentially effectively enough to achieve that degree of helpful spleen and symptom benefit.
Pankit Vachhani, MD: Two things that I would definitely mention here are (1) getting the diagnosis right and (2) risk stratification. Getting the diagnosis right can be frequently challenging when someone is seeing a patient for the first time, making sure that one actually has a case of myelofibrosis and not confusing it with the other myeloproliferative neoplasms, and vice versa.. That I believe is a key factor in the treatment and management of myelofibrosis, ie, getting the diagnosis right. The associated point with that is also differentiation from other causes of fibrosis in patients with other myeloid neoplasms or reactive causes of myelofibrosis. Thus, diagnosis is crucial. I would suggest checking for karyotype as well as a broad NGS [next-generation sequencing] panel at the time of diagnosis on all patients. We have all the data available at baseline. Also, assessing symptom burden is crucial. Many patients who don't complain of symptoms often mention and report symptoms when we go through a more detailed survey of their symptoms using a symptom assessment form. Getting all the baseline parameters as well as symptom burden assessment, ensuring diagnosis, and in selective cases, if possible, maybe even an ultrasound or a CT [computed tomography] scan to assess the spleen volume or spleen length, is very crucial.
Outside of these diagnostic timepoint-related points, the second thing that I think is very crucial in the management of myelofibrosis is risk stratification. Their survival, prognosis, as well as treatment decisions, including but not limited to the JAK inhibitor therapies, but also, for example, the decisions related to stem-cell transplant timing, as well as candidacy for stem-cell transplant in general depend quite a bit on their initial risk stratification. Using the appropriate risk stratification schema, be it the DIPSS [Dynamic International Prognostic Scoring System] or DIPSS plus for patients with primary myelofibrosis or the molecularly enhanced risk stratification schemas like MIPSS70 [Mutation-Enhanced International Prognostic Score System for Transplantation-Age Patients With Primary Myelofibrosis] and MIPSS70-Plus version 2.0 are very crucial. And the counterpoint to that is that in patients with post-ET [essential thrombocythemia] and post-PV [polycythemia vera] myelofibrosis, using the MYSEC-PM [Myelofibrosis Secondary to PV and ET-Prognostic Model] risk stratification schema is very crucial. These are items that really guide us in how we manage the patients right at the point that we see them.
Transcript edited for clarity.