JAK Inhibitors Diversify the Field of Myelofibrosis Symptom and Spleen Management

The wealth of JAK inhibitors available for managing myelofibrosis invites the development of increasingly personalized treatment plans based on individual patient needs and disease characteristics, according to Idoroenyi Amanam, MD.

“We’ve come a long way since ruxolitinib [Jakafi] was FDA approved,” Amanam said in an interview with OncLive^®. “We have a better understanding of which patients benefit from JAK inhibitors, and we are clearer on the shortcomings of JAK inhibitors.”

In the interview, Amanam discussed how JAK inhibitors measure up against other available therapies in myelofibrosis; patient characteristics that are most likely to indicate benefit with JAK inhibitors; and which of these agents he is likely to choose based on patients’ platelet counts, symptom burden, and treatment history.

For instance, Amanam highlighted the importance of pacritinib (Vonjo) in the myelofibrosis treatment paradigm. Pacritinib was approved by the FDA in 2022 for the treatment of select adult patients with intermediate- or high-risk myelofibrosis with thrombocytopenia based on findings from the phase 3 PERSIST-2 trial (NCT02055781), in which 29% patients who received the agent achieved a spleen volume reduction (SVR) of at least 35%. Among patients who received best available therapy, the SVR rate was 3%.¹

He also explained the role of momelotinib (Ojjaara) for patients with anemia. Momelotinib was FDA approved in 2023 for the treatment of adult patients with intermediate- or high-risk myelofibrosis and anemia based on data from the phase 3 MOMENTUM trial (NCT04173494).² In MOMENTUM, 25% of patients who received momelotinib (n = 32/130) experienced a Myelofibrosis Symptom Assessment Form 4.0 total symptom score reduction of at least 50% vs 9% of those who received danazol (Danocrine; n = 6/65), translating to a treatment difference of 16% (95% CI, 6%-26%; P < .0095).³

Amanam is an assistant professor in the Division of Leukemia in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope in Duarte, California.

OncLive: What is the role of JAK inhibitors in the management of myelofibrosis, and how do these agents compare with other available treatment options for this population?

Amanam: Myelofibrosis treatments are divided into 2 different categories. Some myelofibrosis treatments help with symptoms and may help with survival. Other treatments have been proven to be disease-modifying therapies and [may be associated with] more risks in terms of adverse effects [AEs] but might [yield a superior] survival benefit down the.

What patient characteristics and disease factors do you consider when determining whether a patient with myelofibrosis is a suitable candidate for JAK inhibitor therapy?

The first JAK inhibitor that was FDA approved [for patients with myelofibrosis] was ruxolitinib. [This agent] was FDA approved based on 2 factors that were important for patients: symptom benefit and SVR. A patient who is a good candidate for a JAK inhibitor [has] myelofibrosis; a spleen that doesn’t have to be big, but [at least] seems enlarged; and, importantly, a lot of symptoms.

Patients who meet those benchmarks will have a higher chance of experiencing some benefit from the drug compared with patients who may not have an enlarged spleen and may not have symptoms. [Those patients] may come to meet with me and ask if they should start a JAK inhibitor. I have to be honest with them; I’ll tell them [that JAK inhibitors may provide] less of a benefit for them and [could lead to] more AEs.

Which JAK inhibitor do you most commonly reach for in your own clinical practice? What circumstances help you decide between these agents?

Right now, I would divide myelofibrosis into 2 groups: myelofibrosis with platelet counts that are high, and myelofibrosis with counts that are low. If a patient is symptomatic, and their counts are almost normal or on the higher end, I generally tend to use ruxolitinib, especially if they have a high symptom burden. If the patient’s counts are on the lower end and they’re anemic, but they also have a high symptom burden and a large spleen, then I start to consider momelotinib.

If patients’ counts are very low and they are either symptomatic or not symptomatic, or if they have progressed on frontline therapy, I may consider another drug called pacritinib. Another JAK inhibitor [option] is fedratinib [Inrebic]. I generally consider [fedratinib] in patients who either have not achieved a good response with, or are intolerant to, some of the other JAK inhibitors.

References

CTI BioPharma announces FDA accelerated approval of VONJO (pacritinib) for the treatment of adult patients with myelofibrosis and thrombocytopenia. CTI BioPharma Corp. News release. February 28, 2022. Accessed October 8, 2024. https://www.prnewswire.com/news-releases/cti-biopharma-announces-fda-accelerated-approval-of-vonjo-pacritinib-for-the-treatment-of-adult-patients-with-myelofibrosis-and-thrombocytopenia-301492159.html

1. Ojaara (momelotinib) approved in the US as the first and only treatment indicated for myelofibrosis patients with anaemia. News release. GlaxoSmithKline. September 15, 2023. Accessed October 8, 2024. https://www.gsk.com/en-gb/media/press-releases/ojjaara-momelotinib-approved-in-the-us-as-the-first-and-only-treatment-indicated-for-myelofibrosis-patients-with-anaemia
2. Verstovsek S, Gerds AT, Vannuchi AM, et al. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study. Lancet. 2023;401(10373):269-280. doi:10.1016/S0140-6736(22)02036-0