Challenging Disease Features of Myelofibrosis Lead to Use of JAK Inhibitors

Kristen M. Pettit, MD (Moderator)

Clinical Associate Professor

Rogel Cancer Center

University of Michigan Health

Ann Arbor, MI

CASE SUMMARY

• The patient is a 62-year-old man​.
• He presented to his primary care physician (PCP) with symptoms of fatigue, night sweats, and increased bruising​.
• His medical history includes type 2 diabetes, hypercholesterolemia, and hypertension.
• “Normal” physical and blood work 1 year ago​
• His PCP noticed lower hemoglobin (11-9.5 g/dL) and platelet count (350,000/μL-195,000/μL)​ from the previous year’s physical.​
• He was referred to hematology/oncology; first available appointment in 2 months
• At the appointment, exam findings include spleen 5 cm below left costal margin, worsening fatigue and night sweats, and bone pain.
• He has a history of squamous cell carcinoma of the skin.
• Blood: 1% blasts by manual count/flow cytometry
• White blood cells: 19 × 109/L; hemoglobin: 9.1 g/dL; platelets: 135,000/μL; lactate dehydrogenase: 330 U/L
• Bone marrow biopsy showed blasts less than 5% and grade 2/3 fibrosis
• Karyotype was 46,XY [20], and next-generation sequencing panel showed a JAK2 V617F mutation with variable allele frequency of 53%
• ECOG performance status: 2
• Diagnosis: primary myelofibrosis

DISCUSSION QUESTION

In your practice:​

• What patient symptoms prompt you to initiate therapy for MF? ​
• 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? ​

KRISTEN PETTIT, MD: I'm curious to hear how you approach this in your practices, because it's probably a little bit different than what we that what we see here at University of Michigan in the academic setting. We tend to see patients a bit later.

In your practice, what patient's symptoms or findings would prompt you to initiate therapy for a patient with like this with a new diagnosis of myelofibrosis?

SAMER BALLOUZ, MD: Probably constitutional symptoms [such as] fever and night sweats, and splenomegaly. That usually tells me that I have to do something. That is what usually pushes me to start treatment if the patient is otherwise stable with stable [blood cell] counts.

NASHAT GABRAIL, MD: The JAK inhibitors shrink the spleen…I only consider JAK inhibitors for patients with significant splenomegaly.

PETTIT: What do you think that JAK inhibitors leave to be desired?

GABRAIL: To me, the reversal of bone marrow fibrosis is critical in managing myelofibrosis. So far, besides interferon, we don't have any drug that reverses or halts bone marrow fibrosis.

ROBERT BLOOM, MD: If the principal issue is anemia, then one could consider [erythropoietin-stimulating agents or] luspatercept [Reblozyl] because the JAK2 inhibitors don't raise the hemoglobin [level] very well. But if the principal problem is splenomegaly or constitutional symptoms, then they're a good candidate for the JAK2 inhibitors.

GABRAIL: That's a very good point. We assumed that when you shrink the spleen…the hemoglobin will go up. But JAK inhibitors also cause anemia.

IKE ONWERE, MD: That is true for the older therapy, but the newer agents [momelotinib (Ojjaara) and pacritinib (Vonjo)] will improve the hemoglobin and platelet [counts].

ROBERT BLOOM, MD: My impression is that they don't lower it as much, but they do not necessarily improve it.

PETTIT: Thrombocytopenia and anemia are common in patients with myelofibrosis. Thrombocytopenia at the time of diagnosis is present in approximately 25% of patients; severe thrombocytopenia in approximately 11%.¹ It occurs in more than half of patients at some point during their disease course. Anemia is even more common than that at baseline. We see anemia in up to 40% of patients [at baseline] and then at some point during their course in almost all patients with myelofibrosis.²

DISCUSSION QUESTION

• How often do you encounter baseline platelet counts less than 50,000 μL and/or baseline hemoglobin less than 10 g/dL in patients diagnosed with primary myelofibrosis?

PETTIT: Are these common things that you're dealing with in your practice? Are you seeing more of the patients with [enlarged] spleens and terrible symptoms, and not so much with the cytopenias?

ELAINE BEED, MD: I don't see low platelets that often, and I keep looking to see if I can use this agent on it. I don't have very many patients with under 50,000/μL, [although I don’t] have that many patients.

DEEPA JAGTAP, MD: I would echo the same thing. I see more anemia than low platelets as a problem. I have had patients where I've had high platelet count [with] essential thrombocythemia transforming to myelofibrosis. I have [patients with] high platelets and low hemoglobin; that's been a problem for me.

PETTIT: That's helpful to know, and demonstrates that this disease is all over the spectrum. There aren't necessarily 2 patients or 2 practices that are going to be the same.

REFERENCES:

1. Reynolds SB and Pettit K. New approaches to tackle cytopenic myelofibrosis. Hematology Am Soc Hematol Educ Program. 2022;1:235-244. doi:10.1182/hematology.2022000340

2. Tefferi A, Lasho TL, Jimma T, et al. One thousand patients with primary myelofibrosis: the Mayo Clinic experience. Mayo Clin Proc. 2012;87(1):25-33. doi:10.1016/j.mayocp.2011.11.001