Physicians Discuss When to Start Therapy for Primary Myelofibrosis

Abdulraheem Yacoub, MD (MODERATOR)

Professor, Hematologic Malignancies and Cellular Therapeutics

KU Medical Center

The University of Kansas

Kansas City, KS

EVENT REGION: Kansas, Kentucky, Missouri, and Tennessee

PARTICIPANT LIST Shahid Waheed, MD | Michel Bidros, MD | Christiane Zoghbi, MD | Kevin Palka, MD | Anisa Hassan, MD | Phillip Lammers, MD

CASE SUMMARY

A 68-year-old woman presented with symptoms of mild fatigue, moderate night sweats, and abdominal pain and fullness for the past 4 months. She also reported an unexplained weight loss of 12 lb. Her spleen was palpable 8 cm below the left costal margin. She had no known comorbidities.

Laboratory results:

• Red blood cell count: 3.40 × 10¹²/L
• Hemoglobin level: 13.2 g/dL
• Hematocrit: 36%
• Mean corpuscular volume: 94 fL
• White blood cells: 23.0 × 10⁹/L
• Platelets: 450 × 10⁹/L
• Peripheral blood blasts: 1%

Next-generation sequencing showed a JAK2 V617F mutation, and the karyotype was 46XX. A bone marrow biopsy found megakaryocyte proliferation and atypia with evidence of reticulin fibrosis. A blood smear revealed leukoerythroblastosis. She received a diagnosis of primary myelofibrosis (MF), with an intermediate-2 risk according to the Dynamic International Prognostic Scoring System and intermediate risk based on Mutation-Enhanced International Prognostic Score System 70.

DISCUSSION QUESTIONS

• In your experience with MF, which symptoms/ presentations have the most negative impact on patients’ quality of life?
• What is the trigger to initiate therapy for a patient with MF?

YACOUB: In your experience with MF, what are the symptoms of presentation that patients report as most pressing?

WAHEED: The first symptom they bring is anxiety because they come up with [their own] diagnosis, thinking, “This is leukemia,” or “This is some malignant process.” So that’s the first symptom that you have to tackle. Second is their spleen size; they feel fullness in the belly. They’re concerned about blood counts and then what the treatment will be.

YACOUB: Are these concerns defining your goals of care for those patients who present with more symptoms? Are you tackling that more uniquely or separately? Does that guide your choices for therapy?

WAHEED: Yes. You have to discuss with them what are the main symptoms that bother them. For some patients, their spleen doesn’t bother them because of their body habitus. Other patients are more concerned about fatigue or the blood count; others will be more anxious about what is going on in the bone marrow, where it is ending up, the cost of treatment, and the procedures that we’re going to do for the bone marrow and other imaging studies. These are the things you have to take into account and then make a decision with the patient about what you’re going to do. Fortunately, now we have some treatments available for them, rather than supportive care, so you discuss those treatments with them.

YACOUB: That’s a very global approach and very complete. Dr Waheed presented some of the patients’ concerns. Some patients want reassurance, and some patients are low risk…. What are the most common reasons why you have to initiate therapy for those patients?

BIDROS: Symptoms [such as] fatigue, night sweats, early satiety, weight loss, and symptomatic anemia are probably the most commonly presenting symptoms, and this is where I start treatment. If the patient is asymptomatic, I watch and wait.

YACOUB: Do you get a second opinion on every patient? Do you usually take it case by case? Or do you usually feel comfortable managing things yourself?

BIDROS: I cannot send every patient for a second opinion; [I do so] just in complicated cases or if I’m not…very confident of the diagnosis.

YACOUB: How urgent do you feel therapy usually is for a patient with MF? How early do you think we should use therapy?

ZOGHBI: Other [ factors that influence my] approach are age, comorbidities, and my goal of therapy. For example, if a patient is in their early 40s or 50s, even if they are asymptomatic and their blood counts are OK, but they have complex cytogenetics or complex molecular [risk], I may set them up to be evaluated at the university—I work in a community setting—so they have an opportunity if they progress or if they need to be enrolled in a clinical trial. [For] patients who are asymptomatic but who are potential transplant candidates, I send them for evaluation. One common symptom we see is fatigue. Sometimes it is not specific; it could be related to the disease itself or it could be related to the anemia. And abdominal pain, like splenomegaly, is something also that I see commonly requiring treatment early on.

DISCUSSION QUESTION

• What would be your next step in the treatment of this patient?

YACOUB: Almost universally, you would start a JAK inhibitor and refer for SCT [stem cell transplant], which is the standard of care in these patients. If we changed the hemoglobin to 7.8 g/dL— and this is important because myelofibrosis is a disease that is associated with anemia, and treatment is also associated with anemia—we might consider different therapies. This patient is anemic, but she also is losing weight, has a big spleen, and has high-risk disease, so now we have 1 more dimension to juggle. Many of you still think ruxolitinib [Jakafi] or fedratinib [Inrebic] is the standard therapy.

[For those of you who would change therapy in a patient with anemia], what would be your alternative therapy? What do you think you would do differently?

PALKA: When I used ruxolitinib in the past, I had a lot of trouble with anemia, and I don’t treat a lot of this, so I might use fedratinib instead of ruxolitinib and refer for SCT.

YACOUB: Does anybody have a different answer?

HASSAN: I think pacritinib [Vonjo] is the one that we can use in anemia. If I can get the hemoglobin improved, then I could still consider [a] JAK2 [inhibitor]. For a patient at the age of 68, I don’t know if I would want to do a SCT, but still, she’s not that old [for] SCT.

ZOGHBI: Is insurance approving using any of those JAK2 inhibitors before using ruxolitinib? Because sometimes they say you have to use 1 drug before they’ll approve another drug.

YACOUB: They are approved, but that doesn’t mean insurance will not give you a hard time. Even with it approved, they will still give you that statement. One time, I [heard] the excuse that before you use pacritinib, you have to fail hydroxyurea [Hydrea]. They will always give you that hardship, but they’re all approved as first-line therapy.^1-3 You can always appeal, and you will win if you appeal.

DISCUSSION QUESTION

• How do you monitor and manage anemia in patients with primary MF who are receiving a JAK inhibitor?

YACOUB: Let’s talk about your approaches for anemia. Dr Hassan, what is your strategy for monitoring and tackling anemia in patients on JAK inhibitors?

HASSAN: I would try the erythropoietic agents, epoetin alfa [Procrit] or darbepoetin alfa [Aranesp]. Sometimes I get pushback to doing that. If it is necessary, blood transfusion and dose reduction of ruxolitinib are a few things I do.

YACOUB: Dr Lammers, can you go through one of your most recent patients for whom you prescribed ruxolitinib? What is your visit like and [how do you] plan follow-up after they receive ruxolitinib?

LAMMERS: You check erythropoietin [and] also check vitamin levels. Certainly, if iron is low, or [vitamin] B12, or something else, you [manage] that, too. But usually you can find a dose that doesn’t affect the patient’s blood counts too much, in my experience. We can dose reduce and get down to approximately 10 mg twice daily for some patients and not have to transfuse so much.

_REFERENCES

_{1. FDA approves fedratinib for myelofibrosis. FDA. August 16, 2019. Accessed August 13, 2023. https://tinyurl.com/5ej7s4tx}

_{2. FDA approves drug for adults with rare form of bone marrow disorder. FDA. March 1, 2022. Accessed August 13, 2023. https://tinyurl.com/4jcus8km}

_{3. Deisseroth A, Kaminskas E, Grillo J, et al. U.S. Food and Drug Administration approval: ruxolitinib for the treatment of patients with intermediate and high-risk myelofibrosis. Clin Cancer Res. 2012;18(12):3212-3217. doi:10.1158/1078-0432.CCR-12-0653}