NCCN Guidelines Update Adds Momelotinib for High-, Low-Risk Myelofibrosis

Momelotinib has been added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for the treatment of patients with high- and low-risk myelofibrosis (MF) and myelofibrosis with anemia.

MF is part of a group of heterogeneous disorders of the hematopoietic system collectively knowns as Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs). MPNs are considered a rare disease, with the prevalence of MF in the United States estimated to be approximately 13,000, respectively.

Furthermore, MPNs are associated with symptom burdens that result in worse quality of life, functional status, and activities of daily living. Patients with MF are more likely to report symptoms such as fever, night sweats, and weight loss compared with patients with polycythemia vera (PV) or essential thrombocythemia (ET).

Momelotinib is an oral Janus kinase (JAK) 1, JAK2, and activin A receptor type 1 (ACVR1) inhibitor with a recommended dosage of 200 mg orally once daily with or without food. Special considerations for the use of momelotinib also includes risk of major adverse cardiovascular events, thrombosis, and development of malignancies, especially in patients who currently smoke or previously smoked.

The treatment approach for MF is currently identical for primary MF (PMF), post-PV MF, or post-ET MF.

Treatment for lower-risk MF includes momelotinib as a category 2B drug in symptomatic patients. Symptomatic patients may be treated with category 2A drugs, including ruxolitinib, peginterferon alfa-2a, or hydroxyurea, or category 2B momelotinib.

The treatment pathway requires monitoring the response and signs/symptoms of disease progression every 3 to 6 months. For those who respond to the treatment, the guidelines recommend continuing treatment and monitoring. For those with no response or loss of response, the guidelines recommend an alternative option not used for initial treatment, such as momelotinib. The guidelines recommend that patients with disease progression are moved to a higher-risk and accelerated/blast phase MF status.

In patients with high-risk MF, momelotinib was given category 2A status for those with higher platelets (≥50 x 10⁹/L) who were not a transplant candidate; other drugs include ruxolitinib (category 1), fedratinib (category 1), or pacritinib (category 2B). Similarly, the guidelines recommend monitoring patients every 3 to 6 months, continuing treatment for those with a response, recommending a clinical trial or alternative JAK inhibitor not used before for those with no response or loss of response, and accelerated/blast phase MF status for those with disease progression.

For the management of MF-associated anemia, the guideline recommends ruling out coexisting causes, such as bleeding; iron, vitamin B₁₂, or folate deficiency; and hemolysis. After treating coexisting causes, preferred regimens in patients with higher serum erythropoietin (≤500 mU/mL) include clinical trials or momelotinib. Other drugs that may be useful in certain circumstances include danazol, lenalidomide with or without prednisone, thalidomide with or without prednisone, or luspatercept (category 3). Those with a response are recommended to continue treatment, and those with no response or loss of response are recommended to select a treatment other than the one they initially began.

Reference

NCCN. Clinical Practice Guidelines in Oncology. Myeloproliferative neoplasms, version 3.2023. Accessed November 21, 2023. https://www.nccn.org/professionals/physician_gls/pdf/mpn.pdf