Challenging Disease Features of Myelofibrosis Lead to Use of JAK Inhibitors

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