Palmer Discusses Anemia and Transfusion Dependence Concerns in High-Risk Myelofibrosis

Jeanne M. Palmer, MD (MODERATOR)

Vice Chair, Section Chief for Hematology

Program Director, Blood and Marrow Transplant Program

Associate Professor in Medicine

Mayo Clinic

Phoenix, AZ

EVENT REGION California

PARTICIPANT LIST Thomas I. Sweet, MD | Mahshid Melody Mosallaei-Benjamin, MD | Sepehr Rokhsar, MD | Pamela Miel, MD | Sam Yeh, MD | Shirish Mahajan, MD

DISCUSSION QUESTION

• In your experience with myelofibrosis, which symptoms/presentations have the most negative impact on a patient’s quality of life?

SWEET: In my experience, discomfort related to splenomegaly, fatigue, and anemia along with that fatigue are the primary symptoms.

BENJAMIN: I would say fatigue and anemia.

PALMER: Yes; fatigue is tough because sometimes it is independent of anemia, [making it] probably the hardest one to treat. It’s very difficult to make somebody’s fatigue feel any better.

ROKHSAR: I think, similarly, [an impactful symptom is] fatigue. With or without the splenomegaly, there would be a lot of weight loss.

PALMER: Absolutely. Some patients are happy about their weight loss, so it’s always hard to do that symptom score because it says, “How bothersome is this to you?” and they [answer], “I’m not bothered at all. I lost weight.” [However], that’s not the right answer.

MIEL: I would say fatigue, and it’s usually related to anemia.

DISCUSSION QUESTIONS

• What is the trigger to initiate therapy for a patient with myelofibrosis?
• How important is it to initiate therapy early?
• When do you consider clinical trial enrollment?

PALMER: What are the different triggers that make people initiate JAK inhibitor therapy for patients with myelofibrosis?

SWEET: Symptomatic splenomegaly, symptomatic anemia, or fatigue.

MIEL: When you start seeing progressive cytopenia and anemia…then I initiate the conversation on starting treatment.

PALMER: In your experience and opinion, how important is it to initiate therapy early? That is one of those things where there’s been a lot more thought, not only [at] the earlier or lower-risk stages but also even earlier in the symptoms. How do you gauge when to start these treatments? Do you often wait until their splenomegaly becomes more pronounced, or do you do it when you first start to see a hint of it?

BENJAMIN: I [start] when they’re symptomatic, when they start letting me know.… I have a patient who is very anemic but she’s not symptomatic from that. I look at both their subjective symptoms and whether they’re developing thrombocytopenia.

PALMER: When do you consider clinical trial enrollment?

MIEL: Honestly, that wouldn’t be my first thing to think of because I’m out in the community. Most of my patients just want to get started on treatment; they don’t necessarily want to be in a clinical trial. That’s always an option, but if you already have different treatment alternatives or options, you could go with those. Those are standard of care anyhow.

BENJAMIN: Prior to having some treatment options, the clinical trials were definitely a great way to go. And I think [for] people who have lower disease burden, that’s a good place to see whether they would do well on a trial as well, or someone who may have disease progression through other [therapies].

SWEET: The answers [include] referral for stem cell transplant. I would be a little concerned. At the age of 76, I’m not sure I’d necessarily routinely refer that type of patient.

PALMER: We won’t get into the controversy of when you should stop doing stem cell transplants. [According to] the National Comprehensive Cancer Network guidelines, if they’re not a transplant candidate, the category 1 [recommendation] is ruxolitinib [Jakafi] or fedratinib [Inrebic] or clinical trial, momelotinib [Ojjaara], and then [as a category 2B, pacritinib (Vonjo)].¹ At age 76, one could argue they are not, although I know some [centers] that [perform] transplants up to the age of 80 these days. If there’s no response or loss of response, [they recommend] a clinical trial or alternative JAK inhibitor.

CASE UPDATE

The patient is not interested in transplant; a decision was made to initiate momelotinib due to moderate anemia.

DISCUSSION QUESTIONS

• What are the treatment goals for a patient like this?
• If this patient was referred for transplant evaluation, what first-line therapy would you have chosen?

PALMER: What are your treatment goals for this patient?

YEH: [My goals are] to improve symptoms, quality of life, reduce spleen size, and maybe prolong life.

MIEL: [My goal would be] to slow down the progression of anemia; that’s why you would give momelotinib.

PALMER: If the patient was referred for transplant evaluation or decided they wanted a transplant evaluation, would that impact what your first-line therapy would be?

MAHAJAN: No. I don’t know whether there are data to suggest that one of them is superior to the others, so I would still go with ruxolitinib.

PALMER: That’s where most of the data are: for pretransplant ruxolitinib.

DISCUSSION QUESTIONS

• How do the data discussed support or change your approach to treating this patient?
• How do the overall survival (OS) data for momelotinib influence your choice of therapy?

PALMER: Does this change how you would approach treating patients? With a hemoglobin of 13.8 g/dL, I don’t think the momelotinib data would necessarily change [OS]. Do any of these data resonate or change how you would approach treating patients who either have anemia or thrombocytopenia?

MIEL: Yes. In patients who have anemia, with hemoglobin less than 10 g/dL, I would think the treatment of choice would be momelotinib. The data on how it suppresses hepcidin explain how it works in improving hemoglobin levels. The data on outcomes also support using it over ruxolitinib.

PALMER: If you achieve transfusion independence while on momelotinib, you live longer, and…that’s ultimately one of the things that was found, which is why they kept trying to get this approved.² Do [OS] data influence your choice of therapy, especially regarding the transfusion independence, or would that potentially impact who you would choose to put on this drug?

BENJAMIN: It does. I think that’s important. Even if it hadn’t shown survival difference per se, the fact that patients don’t have to go in for transfusions improves their quality of life immensely.³

MIEL: It sounds like if you use momelotinib from the get-go, they had better outcomes in terms of OS [From the Data²]. You could go with ruxolitinib first and then switch, but I think if you just went with momelotinib from the get-go, OS was markedly better.

PALMER: Yes, especially in those who were able to achieve transfusion independence. The bottom line is that if you achieve that transfusion independence and remain transfusion independent, you did quite a bit better.

BENJAMIN: What percentage of patients [achieve] transfusion independence, in your experience?

PALMER: I have several patients who weren’t transfusion independent, and I’ve seen a nice improvement in hemoglobin. It’s been a small number who have been transfusion dependent, whom I put on momelotinib. Most patients I’ve put on momelotinib have been transfusion independent and just develop anemia. I usually use a cutoff of 8 or 9 g/dL for momelotinib. Then I have several patients on ruxolitinib who are still anemic, so I put them on momelotinib.

I just saw one of my patients, and I’ve had her on both ruxolitinib and fedratinib. Either way, she was becoming much more anemic and didn’t have very good spleen response. I just saw her, and she’s been on momelotinib for 2 or 3 months. She’s eating a lot more, her hemoglobin had come up, and she hadn’t been requiring any transfusions. I’ve been very happy with the momelotinib responses, especially with anemia. I would say that, at the very least, I’ve seen very good improvements in hemoglobin.

REFERENCES:

1. NCCN. Clinical Practice Guidelines in Oncology. Myeloproliferative neoplasms, version 1.2024. Accessed June 20, 2024. https://tinyurl.com/yw9ka77m

2. Mesa R, Harrison C, Oh ST, et al. Overall survival in the SIMPLIFY-1 and SIMPLIFY-2 phase 3 trials of momelotinib in patients with myelofibrosis. Leukemia. 2022;36(9):2261-2268. 3. doi:10.1038/s41375-022-01637-7

3. Mesa RA, Kiladjian JJ, Catalano JV, et al. SIMPLIFY-1: a phase III randomized trial of momelotinib versus ruxolitinib in Janus kinase inhibitor-naïve patients with myelofibrosis. J Clin Oncol. 2017;35(34):3844-3850. doi:10.1200/JCO.2017.73.4418