Dr Amanam on Currently Available JAK Inhibitors for Myelofibrosis

Idoroenyi Amanam, MD, assistant professor, Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses 

 in his own clinical practice when treating patients with myelofibrosis and highlights the patient characteristics and disease features that help him decide between these agents in the frontline and relapsed settings.

Amanam categorizes patients with myelofibrosis into 2 main groups based on their platelet counts: those with elevated counts and those with lower counts. For patients with symptoms whose platelet levels are near normal or elevated, Amanam often prefers to use ruxolitinib (Jakafi), especially if the patient has a substantial symptom burden. Amanam notes that ruxolitinib tends to be his go-to option in such cases due to its effectiveness in managing symptoms.

On the other hand, for patients with lower platelet counts who are anemic but still have a high symptom burden and spleen enlargement, he will often consider momelotinib (Ojjaara), he emphasizes. This JAK inhibitor is a suitable treatment option for patients with anemia, as it may offer additional benefits beyond symptom control, Amanam reports.

For patients with severely low platelet counts, regardless of their symptom status, or for those who have progressed on initial therapy, Amanam states that he may turn to pacritinib (Vonjo). Pacritinib is particularly useful in managing myelofibrosis with severe thrombocytopenia, providing an alternative for those who may not be candidates for other treatments, he emphasizes. Lastly, another treatment option to consider is fedratinib (Inrebic), Amanam says, noting that he typically reserves this agent for patients who have either not responded adequately to other JAK inhibitors or are intolerant to them. Fedratinib is an additional therapeutic choice for those who have experienced suboptimal outcomes with previous treatments, ensuring oncologists can tailor therapy to individual patient needs, he concludes.

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Idoroenyi Amanam, MD, discusses the JAK inhibitors he most commonly reaches for in his clinical practice when treating patients with myelofibrosis.

Dr Amanam on the Evolution of Myelofibrosis Management

Idoroenyi Amanam, MD, assistant professor, Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses potential advancements in the management of myelofibrosis to come in the next few years and highlights the use of stem cell transplant in this disease.

In the coming years, advancements in the management of myelofibrosis are likely to focus on combination therapies, particularly those involving a JAK inhibitor paired with a drug that targets proliferative signaling, Amanam begins. These combinations are of great interest within the field, and many oncologists are eagerly awaiting updates from key conferences, he highlights. Beyond combination therapies, the role of cellular therapy is gaining significant attention, according to Amanam. Cellular therapy, long used in managing myelofibrosis through bone marrow and allogeneic transplants, is now being explored in more innovative ways, Amanam reports. These approaches may lead to more precise targeting of the disease, with a focus on identifying new proliferative signaling pathways, understanding the microenvironment, and exploring novel stem cell-based treatments, he notes.

Stem cell transplants are expected to remain a central therapeutic option for patients with myelofibrosis, but with some advancements, Amanam continues. There is now a better understanding of where stem cell transplants work most effectively in managing myelofibrosis, and future research efforts will focus on refining the selection of patients who may benefit from early transplantation, he emphasizes. This decision-making process, however, is becoming more complex as newer therapies emerge, he notes.

The field is currently grappling with the challenge of determining when to proceed with stem cell transplantation vsopting for a novel treatment, Amanam expands. These decisions are not yet definitive, and ongoing research is necessary to guide clinical practice in this regard, he states. Despite these challenges, there is great excitement about the future of myelofibrosis management as new therapeutic avenues are explored and treatment strategies continue to evolve, offering hope for improved outcomes and patient care in the years to come, Amanam concludes.

Idoroenyi Amanam, MD, discusses potential treatment advancements in myelofibrosis and highlights the use of stem cell transplant in this disease.

Dr Amanam on Criteria for Selecting a JAK Inhibitor in Myelofibrosis

Idoroenyi Amanam, MD, assistant professor, Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses the criteria for selecting JAK inhibitors in the treatment of patients with myelofibrosis.

Ruxolitinib (Jakafi) was the first JAK inhibitor approved for the treatment of myelofibrosis by the FDA in 2011

. Amanam notes that this approval was initially based on the agent’s demonstrated benefits in reducing splenomegaly and improving symptom burden, two critical factors that influence treatment outcomes in myelofibrosis. Since then, 3 additional JAK inhibitors have received FDA approval for the treatment of select patients with myelofibrosis: fedratinib (Inrebic) in 2019, pacritinib (Vonjo) in 2022, and momelotinib (Ojjaara) in 2023.

Amanam emphasizes that the ideal candidates for JAK inhibitors are patients experiencing significant symptom burden and splenomegaly. Patients presenting with myelofibrosis, particularly those with moderate to severe spleen enlargement and a high burden of disease-related symptoms, are likely to derive the most benefit from JAK inhibition, he continues.

Conversely, patients who are not experiencing splenomegaly or any symptom burden may have limited therapeutic gain from JAK inhibitors, and the use of these agents in these patients may expose them to unnecessary risks of adverse effects (AEs), he says. The most commonly reported AEs from JAK inhibitor treatment are cytopenias, such as anemia, thrombocytopenia, and leukopenia, Amanam notes.

To avoid these potential toxicities, Amanam stresses the importance of thorough patient evaluation and symptom assessment when considering JAK inhibitors, as the absence of these key criteria can reduce the overall efficacy of treatment and increase the potential for unnecessary AEs.

In clinical practice, Amanam explains the importance of personalized treatment strategies based on individual patient characteristics and risk profiles, prioritizing those who meet the established clinical benchmarks for symptom relief and splenic volume reduction.

Although JAK inhibitors can offer significant symptomatic relief for appropriately selected patients, they are not universally beneficial for all patients with myelofibrosis and should be used judiciously to optimize clinical outcomes, he concludes.

Idoroenyi Amanam, MD, discusses criteria for selecting patients with myelofibrosis who may benefit from JAK inhibitors. 

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.

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

Articles

Dr Amanam on Currently Available JAK Inhibitors for Myelofibrosis

Dr Amanam on the Evolution of Myelofibrosis Management

Dr Amanam on Criteria for Selecting a JAK Inhibitor in Myelofibrosis

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