Dr Amanam on the Optimal Use of JAK Inhibitors in the Current Myelofibrosis Treatment Paradigm

Idoroenyi Amanam, MD, assistant professor, Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses the current treatment paradigm for patients with myelofibrosis, highlighting patients who may derive the most benefit from treatment with JAK inhibitors in this therapeutic landscape.

Current treatments for patients with myelofibrosis can be broadly categorized into 2 groups: those that alleviate symptoms and potentially improve survival, or those classified as disease-modifying therapies, Amanam begins. Although agents in the latter category may confer a long-term survival benefit, they are often associated with a higher risk of adverse effects (AEs), he explains.

The development of ruxolitinib (Jakafi) has greatly improved the management of myelofibrosis, and was the first FDA-approved JAK inhibitor, Amanam states. Its approval was based on data from the phase 3 COMFORT-I and COMFORT-II studies (NCT00952289; NCT00934544) showing symptom relief and reduction in splenic volume, both of which are highly relevant for patients, he notes.

Ideal candidate for a JAK inhibitor like ruxolitinib will typically present with an enlarged spleen and significant symptoms, Amanam continues. Patients who meet both criteria are more likely to experience a meaningful benefit from the treatment, he emphasizes. These benefits may include symptom management and improvement in spleen size, providing enhanced quality of life, Amanam adds.

However, the potential benefits of a JAK inhibitor may be limited for patients who do not meet these criteria, Amanam notes. In such cases, the risks may outweigh the therapeutic benefits. It is crucial to have an open and honest conversation with these patients, explaining that they may not derive as much benefit from JAK inhibitors and could face more AEs, he says. Personalized treatment decisions based on these individual factors can help optimize outcomes for patients with myelofibrosis and minimize unnecessary risks, Amanam concludes.

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Idoroenyi Amanam, MD, discusses the myelofibrosis treatment paradigm, highlighting patients who may derive the most benefit for JAK inhibitor treatment.

Dr Amanam on the Management of AEs Associated With JAK Inhibitors in Myelofibrosis

Idoroenyi Amanam, MD, assistant professor, Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses common adverse effects (AEs) associated with the use of JAK inhibitors in the treatment of patients with myelofibrosis and how these toxicities are managed in clinical practice.

Amanam emphasizes that cytopenias are among the most frequent AEs observed in patients receiving JAK inhibitors, particularly in those with advanced myelofibrosis. Cytopenias, such as anemia, thrombocytopenia, and leukopenia, are anticipated to some extent when initiating JAK inhibitor therapy, he explains; however managing these toxicities required a careful balance, where clinicians must monitor blood counts closely and decide how, when, or if to intervene based on the severity of the cytopenias and the overall clinical benefit to the patient.

The risk of cytopenias in this patient population underscores the importance of monitoring these AEs and adjusting treatment as needed to maintain quality of life and ensure the therapeutic efficacy of the JAK inhibitors, Amanam adds.

Within the current scope of clinical practice, Amanam explains that the initial management of cytopenias involves the careful monitoring of blood cell counts to observe any changes in disease development. Amanam notes that during this step, patient education is important to ensure they understand the potential impact of treatment on their red blood cell, white blood cell, and platelet counts. This up-front discussion is also important in helping to set realistic expectations for patients with myelofibrosis when starting treatment, Amanam says.

In addition to cytopenias, Amanam notes that gastrointestinal (GI) toxicities, including diarrhea, nausea, and abdominal discomfort, are also common AEs observed in patients with myelofibrosis who are being treated with a JAK inhibitor. These GI AEs are managed differently from cytopenias and often require symptomatic treatment.

Although the most commonly observed AEs of JAK inhibitor treatment are cytopenias and GI toxicities, the management of these toxicities depends on the characteristics of each patient. Proactively monitoring patients with myelofibrosis is an essential strategy for mitigating these AEs and optimizing treatment outcomes in the long run, Amanam concludes.

Idoroenyi Amanam, MD, discusses adverse effects associated with JAK inhibitors in myelofibrosis.

Idoroenyi Amanam, MD

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Dr Amanam on the Optimal Use of JAK Inhibitors in the Current Myelofibrosis Treatment Paradigm

Dr Amanam on the Management of AEs Associated With JAK Inhibitors in Myelofibrosis