Pankit Vachhani, MD

Panelists discuss how the future treatment landscape for myeloproliferative neoplasms is evolving with many promising therapies in development, including calreticulin antibodies, selective JAK2 inhibitors, and novel agents targeting various pathways.

Panelists discuss how rusfertide, a hepcidin mimetic peptide, shows promise in polycythemia vera by reducing phlebotomy requirements and potentially improving symptoms by altering iron homeostasis.

Panelists discuss how interferon therapy (particularly ropeginterferon) can provide better hematologic control over time and potentially modify disease progression in polycythemia vera patients.

Panelists discuss how to approach a 67-year-old man with advanced polycythemia vera who is resistant to hydroxyurea, requiring frequent phlebotomies despite maximum tolerated dosing, and experiencing new symptoms like night sweats and fatigue.

Panelists discuss how to monitor patients on JAK inhibitors, including blood count checks every 1 to 2 weeks initially, baseline spleen imaging with follow-up at 3 to 6 months, and symptom burden assessment.

Panelists discuss how to select among the four available JAK inhibitors (Ruxolitinib, Fedratinib, Pacritinib, and Momelotinib) based on patient-specific factors such as anemia, thrombocytopenia, and symptom burden.

Panelists discuss how JAK inhibitor therapy can benefit patients with intermediate-1–risk myelofibrosis despite being studied primarily in higher-risk patients in the COMFORT and JUMP trials.

Panelists discuss how risk stratification, symptom burden, and splenomegaly guide treatment decisions for a 68-year-old woman with intermediate-risk myelofibrosis who isn’t interested in transplant.

Panelists discuss how new treatments like rusfertide (a hepcidin mimetic) offer promising options for polycythemia vera patients, demonstrating benefits in reducing phlebotomy requirements while addressing the paradoxical iron deficiency caused by current treatments, potentially improving quality of life while allowing patients to maintain their existing cytoreductive therapies, though questions remain about whether it will show the disease-modifying effects seen with ruxolitinib and interferons.

Panelists discuss how interferon therapy for polycythemia vera requires patient education about its unique characteristics, including the need for long-term treatment (with benefits most apparent at 36 months rather than 12 months), potential adverse effects (mild flu-like symptoms, depression, injection site reactions, and autoimmune issues), and evolving dosing strategies that may improve tolerability, while emphasizing that with FDA approval of ropeginterferon, insurance hurdles have decreased and molecular response monitoring may eventually guide treatment optimization.

Panelists discuss how the MAJIC-PV trial provides critical evidence that ruxolitinib offers more than symptomatic relief in polycythemia vera, demonstrating approximately 40% reduction in thromboembolic events and improved event-free survival while correlating these clinical benefits with molecular responses through JAK2 V617F allele burden reduction, suggesting ruxolitinib may be truly disease-modifying rather than merely a bandage treatment when comprehensive control of all 3 blood cell lineages (red cells, white cells, and platelets) is achieved.

Panelists discuss how ruxolitinib provides comprehensive benefits for polycythemia vera patients beyond count control, highlighting its remarkable ability to rapidly alleviate severe pruritus (often within 48 hours) and other constitutional symptoms that remain resistant to conventional therapies like hydroxyurea and interferon while also effectively managing cytokine-driven and spleen-related symptoms that significantly impact quality of life.

Panelists discuss how the CYTO-PV study provides compelling evidence for maintaining strict hematocrit control below 45% in polycythemia vera patients, demonstrating that even a 3% difference in hematocrit levels can lead to a fourfold increase in cardiovascular events and thrombosis risk while also emphasizing the independent importance of controlling white blood cell counts below 11 × 109/L to further reduce thrombotic complications.

Panelists discuss how multiple pivotal clinical trials inform polycythemia vera management strategies, highlighting key findings from CYTO-PV (strict hematocrit control <45% reduces thrombosis risk fourfold), RESPONSE (ruxolitinib’s superiority over best available therapy for controlling both hematocrit and splenomegaly), MAJIC-PV (demonstrating improved event-free survival with ruxolitinib), and PROUD-PV/CONTINUATION-PV (showing ropeginterferon’s durable molecular responses compared with hydroxyurea’s diminishing effect over time).

Panelists discuss how managing advanced polycythemia vera requires tailored approaches beyond hydroxyurea when patients show resistance (persistent hematocrit >45%, elevated white blood cell counts, ongoing symptoms), with experts advocating for either second-line ruxolitinib for rapid symptom and hematologic control or interferons (particularly in younger patients), while emphasizing the importance of addressing modifiable cardiovascular risk factors like smoking cessation.

Panelists discuss how polycythemia vera treatment follows a risk-stratified approach, with all patients receiving daily aspirin and phlebotomies to maintain hematocrit below 45%, while high-risk patients (aged >60 years or history of thromboembolism) additionally require cytoreductive therapy with options including hydroxyurea, pegylated interferon alfa-2a, ropeginterferon alfa-2b, or second-line ruxolitinib, with treatment modifications based on response, tolerance, and disease progression.

Panelists discuss how the MOMENTUM trial demonstrated momelotinib’s superiority over danazol in symptomatic anemic myelofibrosis patients, showing significant improvements in symptoms (the primary end point), meaningful spleen volume reduction (SVR25/SVR35), and anemia benefits, with experts noting that the inclusion of a washout period provided clearer evidence of momelotinib’s efficacy profile compared to the SIMPLIFY-2 trial.

Panelists discuss how second-line treatment decisions for myelofibrosis patients failing ruxolitinib can be guided by clinical trial data such as that from SIMPLIFY-2, whereas momelotinib offers comparable spleen control with superior anemia benefits and potential symptom improvement, although experts emphasize the importance of considering a patient’s specific failure pattern and setting appropriate expectations when switching therapies.

Panelists discuss how Janus kinase (JAK) inhibitors like pacritinib offer crucial treatment options for myelofibrosis patients with severe thrombocytopenia (platelet counts <50,000 ), highlighting its advantages in providing significant spleen volume reduction (29% vs 3% in PERSIST-2 trial) while also offering unexpected anemia benefits possibly due to ACVR1 inhibition, with clinicians noting they set realistic expectations about platelet stabilization rather than improvement when counseling patients.

Panelists discuss how Janus kinase (JAK) inhibitor dosing strategies must be carefully tailored for anemic myelofibrosis patients, with clinical experience suggesting starting at lower doses (10 mg twice daily ) and gradually escalating based on the REALIZE trial approach, while balancing efficacy goals against cytopenia risks and monitoring unique toxicity profiles of different JAK inhibitors including Wernicke encephalopathy with fedratinib and gastrointestinal issues with pacritinib.

Panelists discuss how clinical trial data from the COMFORT studies supports using Janus kinase (JAK) inhibitors such as ruxolitinib for myelofibrosis patients beyond the original high-risk study population, with experts noting they often treat intermediate-1-risk patients based on symptomatic burden and splenomegaly rather than risk stratification alone to achieve meaningful spleen volume reduction and symptom improvement.

Panelists discuss how treatment goals for intermediate-risk myelofibrosis patients focus on achieving meaningful clinical outcomes including relieving symptoms, preventing worsening of anemia, maintaining transfusion independence, reducing symptomatic splenomegaly, and ultimately improving survival while considering patient-specific factors like age and transplant eligibility.

Panelists discuss how treatment selection among Janus kinase (JAK) inhibitors for myelofibrosis involves considering specific patient characteristics such as cytopenia profiles, mutation status, risk stratification using MIPS criteria, and balancing potential transplant candidacy with careful timing of JAK inhibitor therapy.

Panelists discuss how advancements in understanding myeloproliferative neoplasms are shaping treatment approaches through case studies of intermediate-risk myelofibrosis and advanced polycythemia vera, with emphasis on Janus kinase (JAK) inhibitor selection based on genetic profiles and patient-specific factors.

The field of mastocytosis is witnessing a paradigm shift with precision medicine in the form of mutant KIT inhibitors.

Closing out their discussion on the management of myeloproliferative neoplasms, Rami S. Komrokji, MD, and Pankit Vachhani, MD, look toward the future treatment paradigm.

Key opinion leaders provide a comprehensive review of agents under investigation, alone or in combination, in patients with myelofibrosis.

Focusing on real-world management of myelofibrosis, experts share insight on how they would select and sequence therapies within the current paradigm.

A review of the treatment armamentarium for patients with myelofibrosis in the context of clinical trial data supporting use of these agents.

Shifting their attention to myelofibrosis, Rami S. Komrokji, MD, and Pankit Vachhani, MD, define differences between various subsets of disease.