Challenging Disease Features of Myelofibrosis Lead to Use of JAK Inhibitors
During a Case-Based Roundtable® event, Kristen Pettit, MD, moderated a discussion on which disease features of myelofibrosis are most challenging and when to use JAK inhibitors in the first article of a 2-part series.
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
In practice, what is the most difficult disease feature to manage in 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.
