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Raajit K. Rampal, MD, PhD, discusses symptom management in patients with myelofibrosis, defining disease progression, and key considerations for starting or delaying treatment.
JAK inhibitors represent a key weapon in the myelofibrosis arsenal when it comes to managing symptoms associated with the disease, according to Raajit K. Rampal, MD, PhD, who added that although challenges remain with regard to defining disease progression and determining when treatment should be initiated in certain patients, novel agents in the pipeline may help to further improve outcomes.
“The management of myelofibrosis is not necessarily black and white. There are shades of grey in terms of trying to figure out who needs treatment, when they need it, and what they should receive. There is some nuance there, but the good news is that we have options,” Rampal said. “It is important to know that several promising agents are under Investigation, including many agents in late-stage trials. We are in a far better place than we were 5 years ago. Hopefully, these drugs will get approved, and most importantly, [improve] outcomes for our patients.”
In an interview with OncLive®, Rampal, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, discussed symptom management in patients with myelofibrosis, defining disease progression, and key considerations for starting or delaying treatment.
Rampal: To treat symptoms in patients with myelofibrosis, we often use therapies such as JAK inhibitors. Of course, this depends on the symptoms. Principally, we are talking about symptoms that many patients experience, such as fatigue, night sweats, fevers, early satiety, and abdominal discomfort. In multiple studies, JAK inhibitors have been shown to have an important impact on that symptom burden. Oftentimes, that is our major intervention to try to alleviate those symptoms [for patients].
I am not sure that we necessarily have a uniform definition for disease progression. However, we do know that [progression] encompasses certain things. When breaking it down, [the first thing to consider are] the symptoms, and patient-reported symptoms are a component of this. For example, if patients have been stable on [treatment with a] JAK inhibitor and suddenly they are experience recurrence of their initial symptoms, or potentially even new symptoms, then that can be consistent with symptomatic disease progression.
When we consider this on a hematologic level, what are the things that would indicate to us that we have a problem? If we have a patient who has been stable on therapy, and now their platelet count is starting to fall, or their hemoglobin is starting to fall, they need transfusions and they had not previously been transfusion dependent, and they have been on their JAK inhibitor for 6 months or more—those are all the things that would be worrisome to us. That is a sign that the bone marrow is not functioning as well as it used to.
Other things that we worry about from a blood perspective, is, for example, if we start to see an increasing number of circulating blasts; that is also potentially an indicator of progression to an accelerated phase, or even beyond that. Scans sometimes help us. If a patient has had a clinically stable spleen or liver size, and upon exam [we see] it is a little bit larger, and then we radiographically confirm that there has been an increase in size, then that is also consistent with progression.
[The decision] is a little bit more straightforward in a patient who has not been previously treated. However, if there is evidence that a patient’s disease is progressing or accelerating, is it a black or white decision in terms of when to start treatment? No. It depends on what the symptom burden is, or what the disease findings are. Obviously, if a patient has a spleen that is enlarging, and that is causing them symptoms, then that is a reason to start to treat them. If a patient reports that they are mildly more fatigued than usual, but their blood counts are stable, they otherwise feel well, and [the symptoms are] not impacting their quality of life, then that may be a reason not to treat [them right away]. It really depends on the degree of symptoms. However, in some cases, it is very clear when it is time to treat someone.
Regarding patients who are on active treatment, [this situation was historically] more difficult. For example, if we had someone who was on ruxolitinib [Jakafi] and doing fine, and then suddenly their symptoms and disease started to progress, a few years ago, we would have very few options [to offer them] aside from clinical trials or taking the patient to transplant. The advent of fedratinib [Inrebic] as a potential second-line therapy has changed things. We know we have a second-line option that we can go to that has a reasonable chance of improving symptoms and spleen size. Regardless, we must always be vigilant regarding evidence of disease progression—whether someone is on treatment or they have not yet started treatment. In either case, there are things that we can do to intervene and help them.
It is challenging. We are glad to have these options, but is there a clear-cut reason to use 1 drug over the other? In most cases, the answer is no. [However,] there are some select cases where we can think differently. For example, the dosing of ruxolitinib is based on platelet [counts], and we lower the dose if the platelets are lower, particularly if patients have platelet counts of 50,000 to 100,000. With fedratinib, that is not the case. We can use the same dose, regardless of the platelet count, as long as it is above 50,000. In select patients, it may make more sense to use a drug like fedratinib in those who have platelet counts of less than 100,000 because we can use the full dose of the drug. However, in patients with a higher platelet count, it might not make so much of a difference.
[Additionally,] it is important to discuss the potential adverse effects [AEs] with patients. We do see more gastrointestinal AEs with fedratinib, relatively speaking. Discussing potential AEs with the patients is always an important part of that conversation.