During a Targeted Oncology™ Case-Based Roundtable™ event, Haris Ali, MD, and participants discussed approaches to starting JAK inhibitor therapy for a patient with myelofibrosis and when to refer for stem cell transplant. This is the first of 2 articles based on this event.
HARIS ALI, MD: In your practice, what is the trigger to initiate therapy for a patient with newly diagnosed myelofibrosis? What would be the timing to start JAK inhibitor therapy? And how do you choose?
DRAUPADI TALREJA, MD: It depends on anemia, fatigue, how big their spleen is, and how much discomfort they have from the splenomegaly. Those are my initiating factors for the treatment.
HARIS ALI, MD: So [you use] a combination of all things: anemia, symptoms, and enlarged spleen.
TALREJA: [It would need to be] not just a mild splenomegaly but a big spleen, moderate to severe. I see patients with moderate splenomegaly quite a bit. Minimal splenomegaly doesn't cause many symptoms. That’s been my experience.
IMA WONG, MD: I think the blood counts also play a role because of the cytopenia, even though symptoms are definitely also an important part for the physician [to consider].
ALI: Symptoms, spleen, and cytopenias: all of these factors play a role [in starting] the initial therapy. How important it is to initiate therapy early? For a patient presenting, would you consider starting therapy early or would you wait at certain threshold of cytopenia, symptoms, and spleen [size] to start treatment?
ARATI CHAND, MD: I think it's important to start treatment early because it's also important to figure out if this patient needs to be evaluated for stem cell transplant [SCT], or if the patient should be on treatment for symptom control. What are the long-term goals for this patient? If someone is very symptomatic, that's easy. But if the patient has minimal to no symptoms, and just has a high white blood cell count, or something like that, it is trickier because I think the patients should be evaluated for possible cure with SCT, rather than just putting the patient on a treatment indefinitely. I think if the patient is not an SCT candidate or does not want to pursue an SCT, then I prefer to start early. It's better to prevent or delay the onset of symptoms, rather than wait for the patient to get symptomatic, and then try to fix the anemia and thrombocytopenia with the splenomegaly, because all those symptoms are bound to happen. It's just a matter of time.
ALI: That is a very important point. Would you consider referring all patients who look potentially transplant eligible, even at the beginning, to look for the SCT option? Or would you consider it once your treatment [starts]? How would you decide?
CHAND: I usually send my younger patients for an evaluation early on in the course of diagnosis. If they're 80 years or older, I don't send them for an SCT evaluation because I know they're not going make it to SCT. But I send my younger patients, in their 70s, for SCT evaluation as early as I can. If they are symptomatic, I will start treatment. There are sometimes [obstacles due to] real-world authorization and scheduling; everything takes time, and I don't think people should wait on treatment just to get the evaluation. I will sometimes start treatment and then try to get them [evaluated for] SCT during the course of the treatment.
SWARNA CHANDURI, MD: For most of the patients, I wait for the symptoms and the cytopenias before I start them on any of these treatments. I'll encourage them when they receive diagnosis to have a consultation with a tertiary center to see if they are candidates for SCT early on. I have 2 of [these patients now]. They're young, but they have cytopenias and bone marrow biopsy confirms that it is myelofibrosis; spleen is marginal, but they are asymptomatic. I haven't started them on any treatment. I'm still observing, and I sent them for transplant evaluation. They didn't give any recommendation, just a follow-up at this point, unless something new has changed.
ALI: Right now, a lot of new drugs are being tried and new pathways are being explored for treatment, starting from patients with newly diagnosed disease where you add a novel agent to a JAK inhibitor. Maybe someone with a partial response will [receive] an add-on treatment, or maybe a patient who is JAK inhibitor refractory, and a new drug being tried. Patients should definitely be considered for SCT but any stage of disease may be considered for clinical trials because a lot of new agents are currently being tried in these patients with a varying degree of success.
What would be your next step for a patient with myelofibrosis aged 76 who has enlarged spleen, constitutional symptoms, and moderate anemia?
ALBERT DEKKER, MD: [The goals are] prolongation of life and prevention of complications. Do you believe that there is a place for fedratinib [Inrebic] in this day and age with alternative JAK inhibitors?
ALI: It's a very good question. In my practice, I don't have too many patients on fedratinib and I'm very comfortable with using ruxolitinib [Jakafi]. Now we've added pacritinib [Vonjo] for thrombocytopenia and momelotinib [Ojjaara] for patients with anemia. I see fewer patients on fedratinib in my practice. Do you use fedratinib a lot?
TALREJA: I don't because I don't think it is better than ruxolitinib. I think it's about the same, and we have better drugs than fedratinib. Momelotinib is much better than fedratinib, but pacritinib is only for patients with a low platelet count. I think momelotinib is a far superior drug than what we have right now for myelofibrosis.
CHAND: I used fedratinib once and the patient had such terrible diarrhea, they begged me to come off the drug, and there was no way she could continue on the medication. After that, I have never used it.
ALI: We have less and less room for an indication that you can find to use fedratinib on your patients with the current options available.
ALI: What first-line therapy would you have chosen? [In the poll], a majority of the participants selected ruxolitinib.
TALREJA: But that was not for SCT. That was because of the big spleen and the [other issues]. If you wanted to do [SCT], the best drug for this patient would be momelotinib, to decrease the myelofibrosis, decrease the spleen size, get improvement of anemia, and get the patient in the best physical state for the transplant.
ALI: That's a very good option. Momelotinib addresses all 3 problems, including the cytopenia, anemia, and then [you could] refer to SCT. Would everyone choose momelotinib or would you use some other agent if this patient you're eventually would refer for transplant?
CHANDURI: I'm not familiar with this new drug. The only drug I [am familiar with is ruxolitinib], so to answer that question, I don't know.
CANDICE RUBY, MD: [I would probably choose] momelotinib. One of the things is, when patients [discontinue] ruxolitinib, they have a flare-up.1 So I would choose momelotinib.
1. Palandri F, Palumbo GA, Elli EM, et al. Ruxolitinib discontinuation syndrome: incidence, risk factors, and management in 251 patients with myelofibrosis. Blood Cancer J. 2021;11(1):4. doi:10.1038/s41408-020-00392-1