Cytopenias and Symptoms Prompt Imitation of JAK Inhibitors in MF

Gabriela S. Hobbs, MD

Assistant Professor of Medicine

Harvard Medical School

Clinical Director of Leukemia

Massachusetts General Hospital

Boston, MA

GABRIELA HOBBS, MD: In practice, what is the most difficult disease feature to manage in primary myelofibrosis? Is it thrombocytopenia, anemia, splenomegaly, constitutional symptoms or other? For anybody who said anemia or thrombocytopenia, do you want to comment on why those are challenging?

NASFAT SHEHADEH, MD: I chose anemia. Usually, patients have more symptoms related to anemia than thrombocytopenia, so they probably come to our attention more than thrombocytopenia. Obviously, thrombocytopenia can be a challenge during the treatment…but it is the anemia that I find challenging, because usually once the patient hits low hemoglobin, they become symptomatic, and we try to avoid a transfusion if possible. I find that anemia is more challenging than thrombocytopenia at the beginning.

HOBBS: That's a great point. Anemia is something that's more likely to immediately impact quality of life from the symptoms that it causes, as well as the time spent in clinic.

RAGHAVA INDURU, MD: For myself, especially in the patients that I have, thrombocytopenia tends to be the most challenging for us, because some of our patients’ [platelet counts] are [less than 20,000/μL] or sometimes even less than 10,000/μL and we struggle because transfusions don't work a lot, and a lot of them have other medical comorbidities…especially older patients. These are the challenges that we deal with, and thrombocytopenia is further complicating the picture. Anemia is potentially challenging, but thrombocytopenia is something that makes it difficult.

ATTIQUE SAMDANI, MD: I've seen a few patients, but the last 2 patients have had issues with constitutional symptoms. Even though their numbers don't translate into that much anemia, and even though the numbers improved, [whether due to] the medicine [or] the disease itself, one of them keeps on asking for prolonging his disability or his time off from work.

HOBBS: So sometimes there's a disconnect between what the blood counts are showing with how the patients are feeling. I think that's pretty common. So that's a great point.

NIYATI NATHWANI, MD: I picked constitution symptoms because fatigue [and others] are so subjective, and I feel those are difficult. Even for patients with profound thrombocytopenia and anemia, we have now drugs available to target those with pacritinib [Vonjo] and momelotinib [Ojjaara], but I feel constitutional [symptoms are challenging] for me. Some of them are younger patients [who] want to keep on a working schedule. Because that's so subjective, I feel that would be the hardest for me.

HOBBS: That's a wonderful point. Sometimes the JAK inhibitors really help with the constitutional symptoms, but they don't always work all the way and like [Dr Samdani] mentioned, sometimes the numbers don't tell the full story, and especially for our younger working patients, fatigue can be a really debilitating symptom that keeps people from working, especially those young patients that are still working.

DISCUSSION QUESTIONS

In your practice:​

• What patient symptoms prompt you to initiate therapy for myelofibrosis? ​
• What symptoms are the most important to control? ​
• When do you start JAK inhibitor therapy?​
• Do you choose your initial JAK inhibitor based on patient symptoms? ​

HOBBS: What are the symptoms that will prompt you to initiate therapy with myelofibrosis? How do you decide who needs to get started on therapy?

NASFAT SHEHADEH, MD: Symptoms will [make me] decide; if the patient has a lot of constituent symptoms, then I will initiate, plus the blood counts. The symptoms and the blood count issues, and sometimes they're related—if somebody has significant anemia, they might have hemoglobin of 9 to 10 g/dL, but they have a lot of constitutional symptoms, like night sweats, fever, and splenomegaly.

HOBBS: And what's the first drug you use?

SHEHADEH: The first drug is determined by the blood count. Usually, if their platelet count above 50,000/μL, you can go with ruxolitinib [Jakafi]. If the hemoglobin is down, you can now use momelotinib for patient with significant anemia.

HOBBS: Does anybody have a different approach to initial therapy [besides looking at] blood counts and symptoms, and choosing a JAK inhibitor based on the blood counts?

RAGHAVA INDURU, MD: I have a similar situation as well. I have 1 or 2 patients who have such an indolent disease, even though they do have cytopenias, but because of lack of symptoms, I didn't start them on treatment. I've been following them, but it's predominantly because of cytopenias.

This patient has the platelet count running in the low 20,000s [per μL], but they don't have symptoms for the last at least 5 years I've been following him. For someone like that, [I consider] their goals of care as well, if someone is extremely anxious, worried, and concerned, vs someone who might be weighing in the adverse events of the treatment, or weighing in the risk and benefit and decide that they're comfortable closely being followed. I think that’s part of the discussion that comes into play. When I do start treatment…platelet count is something that I do consider. Usually, my go-to is ruxolitinib, but I had someone recently with post essential thrombocythemia myelofibrosis where I considered fedratinib [Inrebic].

HOBBS: Tell us about that [experience].

INDURU: I just started. I want to see how it goes.

HOBBS: Sounds great. It is approved in first line, so it's not a wrong choice for sure, and it's OK to try it there, even though we're all probably more familiar with ruxolitinib.

INDURU: His choice was because of the dosing. It's once a day dosing with fedratinib, compared with twice a day [ruxolitinib], and he's someone who works in construction for long hours, so he preferred it once a day.^1,2

HOBBS: Yes, totally reasonable.

REFERENCES:

1. Inrebic. Prescribing information. Bristol-Myers Squibb; 2023. Accessed August 14, 2024. https://tinyurl.com/ms6emc6k

2. Jakafi. Prescribing information. Incyte Corporation; 2023. Accessed August 14, 2024. https://tinyurl.com/ua3rzhwr