Andrew Kuykendall, MD

Panelists discuss how differentiating primary from secondary erythrocytosis is crucial in guiding treatment strategies, emphasizing the importance of addressing underlying causes such as chronic hypoxia, tumors, or anabolic steroid use while managing hematologic parameters as necessary.

Panelists discuss how the future of polycythemia vera (PV) management will be shaped by advancements in targeted therapies, precision medicine, and symptom control, with innovations such as next-generation JAK inhibitors, hepcidin mimetics like rusfertide, gene therapies, and personalized treatment approaches offering more effective, tailored, and holistic management options that improve disease control and quality of life for patients.

Panelists discuss how hepcidin mimetics like rusfertide complement existing therapies in polycythemia vera (PV) by regulating iron metabolism, reducing iron overload, and balancing erythropoiesis, which can enhance the effectiveness of cytoreductive treatments, alleviate symptoms like fatigue and splenomegaly, and improve quality of life, particularly in patients with refractory disease or those requiring frequent phlebotomy.

Panelists discuss how hepcidin mimetics like rusfertide offer a novel approach to managing polycythemia vera (PV) by regulating iron metabolism, reducing iron overload, and improving hematocrit control, particularly in patients with iron deficiency or refractory disease, while also potentially enhancing disease management and quality of life when used alone or in combination with standard therapies like hydroxyurea or ruxolitinib.

Panelists discuss how clinical trial data has shaped second-line therapy in polycythemia vera (PV), highlighting ruxolitinib and interferon as key options for patients resistant or intolerant to hydroxyurea due to their efficacy in symptom control, quality of life improvement, and disease-modifying benefits, especially for those with splenomegaly or inadequate response to first-line treatments.

Panelists discuss how JAK inhibitor therapy, while effective in treating myelofibrosis and other hematologic disorders, increases the risk of skin cancers, particularly non-melanoma skin cancers, and emphasize the importance of regular screening, patient education, and preventive measures to manage this risk.

Panelists discuss how the evolution of myelofibrosis care has led to advancements in pharmacotherapy, risk stratification, and emerging therapies while highlighting ongoing unmet needs such as long-term disease control, treatment resistance, anemia and thrombocytopenia management, and the need for personalized treatment approaches.

Panelists discuss how in polycythemia vera (PV), when standard cytoreductive therapies fail to control symptoms, targeted treatments such as ruxolitinib for pruritus and splenomegaly, iron supplementation for fatigue, nonsteroidal anti-inflammatory drugs (NSAIDs) for pain, and psychosocial support play a crucial role in improving symptom management and enhancing patient quality of life.

Panelists discuss how in polycythemia vera (PV), effective management involves a dual focus on thrombosis prevention with aspirin, phlebotomy, and cytoreductive therapy, alongside strategies for managing symptoms like fatigue, pruritus, and splenomegaly, while regular assessments of quality of life and psychosocial support are essential for enhancing patient well-being.

Panelists discuss how important end points for evaluating new myelofibrosis therapies include overall survival, symptom improvement, splenic volume reduction, hematologic parameters, disease modification, safety, and patient-reported outcomes, all of which help assess the impact of treatment on both clinical outcomes and quality of life.

Panelists discuss how investigational therapies beyond Janus kinase (JAK) inhibition, including epigenetic modulation, telomerase inhibition, PI3K/AKT/mTOR pathway inhibition, immune modulation, TGF-β inhibition, and novel anti-fibrotic agents, are showing promise in improving efficacy and targeting different disease pathways in myelofibrosis.

Panelists discuss how in polycythemia vera (PV), defining and managing treatment resistance or intolerance is crucial, requiring careful monitoring and timely intervention, including assessing adherence, evaluating mutations, and making therapeutic adjustments such as dose modifications, switching to alternative therapies like ruxolitinib or interferon, and employing a multidisciplinary approach to ensure optimal disease control and patient outcomes.

Panelists discuss how the choice between hydroxyurea (HU) and interferon (IFN) for cytoreductive therapy in polycythemia vera (PV) depends on factors such as patient age, long-term safety, tolerability, comorbidities, response to previous treatments, and patient preferences, with HU often preferred in older patients and IFN favored for younger patients, those intolerant to HU, or those seeking potential disease-modifying effects.

Andrew Kuykendall, MD, discusses data from a phase 2 trial of fedratinib for the treatment of myeloproliferative neoplasms.

Panelists discuss how managing myelofibrosis patients with challenging cytopenias involves careful treatment selection, regular monitoring of blood counts, and tailored dose adjustments to balance disease control with the risks of exacerbating hematologic toxicities.

Panelists discuss how selecting and optimizing Janus kinase (JAK) inhibitor therapy in myelofibrosis involves personalizing treatment based on patient risk factors, comorbidities, and preferences while emphasizing regular monitoring to manage adverse effects and improve quality of life.

Panelists discuss how frequent phlebotomy requirements—typically more than 4 to 6 times per year—serve as a marker of inadequate disease control in polycythemia vera (PV), prompting consideration of cytoreductive therapy to improve hematologic stability, alleviate symptoms, and reduce thrombotic risk.

Panelists discuss how the decision to initiate cytoreductive therapy in polycythemia vera (PV) is driven by high-risk features such as age over 60 and thrombotic history, as well as factors like inadequate hematocrit control, symptom burden, and intolerance to phlebotomy, with therapy tailored to individual patient needs and goals.

Panelists discuss how managing asymptomatic splenomegaly in myelofibrosis requires a nuanced approach, balancing observation in low-risk patients with early intervention using Janus kinase (JAK) inhibitors in higher-risk cases, while emphasizing the importance of regular monitoring, patient preferences, and shared decision-making.

Panelists discuss how survival data from the COMFORT trials support the use of ruxolitinib in myelofibrosis, especially in intermediate- to high-risk patients with significant symptom burden or splenomegaly, while highlighting the need to consider patient selection, crossover effects, and real-world applicability when interpreting these results.

Panelists discuss how thrombotic risk assessment—anchored in age, thrombotic history, and additional factors like leukocytosis and JAK2 allele burden—guides personalized therapy in polycythemia vera (PV), balancing cytoreduction, symptom control, and prevention of vascular events.

Panelists discuss how integrating molecular markers—particularly JAK2 V617F allele burden—and clinical features such as symptom burden and thrombotic history inform diagnosis, risk stratification, and monitoring strategies in polycythemia vera to anticipate disease progression and guide personalized treatment.

Panelists discuss how initiating therapy in myelofibrosis requires a personalized approach that balances symptom burden, risk stratification, cytopenias, and patient goals, with treatment decisions—often involving Janus kinase (JAK) inhibitors—tailored to optimize both disease control and quality of life.

Panelists discuss how accurate risk stratification using clinical and molecular prognostic tools like DIPSS, MIPSS70, and GIPSS guides personalized treatment decisions in myelofibrosis, ranging from observation in low-risk patients to Janus kinase (JAK) inhibitor therapy and early transplant evaluation in higher-risk cases.

Panelists discuss how distinguishing pre-fibrotic myelofibrosis from other myeloproliferative neoplasms like essential thrombocythemia remains challenging due to overlapping clinical and molecular features, subjective histopathologic interpretation, and variable application of diagnostic criteria, underscoring the need for expert pathology review and multidisciplinary evaluation to guide accurate diagnosis and management.

Panelists discuss how evolving insights into myelofibrosis—driven by molecular profiling, risk-adaptive therapy, and emerging treatments—are reshaping clinical practice toward more personalized care, with increasing focus on managing cytopenias, treatment resistance, and long-term disease modification.

Andrew Kuykendall, MD, discusses the background, methods, and design of a phase 2 study which evaluated fedratinib.

Andrew Kuykendall, MD, discusses the rationale behind choosing to evaluate fedratinib in a phase 2 study for patients with atypical chronic myeloid leukemia, chronic neutrophilic leukemia, MDS/MPN-unclassifiable, and MDS/MPN-ring sideroblasts and thrombocytosis.

Dr. Kuykendall provides his perspective on the biggest unmet needs with current advanced PV therapies, emerging data he is following that may impact future management, and any other clinical pearls for optimal PV management.