In this interview, Harrison discusses key findings from Arm 3 of the trial (NCT04176198), which enrolled patients who had been previously treated with a Janus kinase inhibitor (JAKi) other than momelotinib. The study aimed to identify the recommended phase II dose (RP2D) of nuvisertib when administered in combination with momelotinib, and to assess the safety, clinical activity (spleen volume reduction [SVR] and total symptom score [TSS] improvement), and pharmacokinetics and pharmacodynamic markers (including cytokines and bone marrow fibrosis).

This educational resource is independently supported by Sumitomo. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.

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In this interview, Kiladjian first provided an overview of the phase III ROP-ET (NCT06514807) study design and key patient eligibility criteria. He then discussed the primary endpoint results, highlighting that the ROP-ET study met the primary endpoint – a composite durable hematologic and clinical response after 12 months. Finally, Kiladjian explored the safety profile of ropeginterferon alfa-2b observed in the study.

This educational resource is independently supported by AOP Health. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource. 

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In this interview, Vaughn discusses the potential benefits of an extended-release ruxolitinib formulation for patients with myelofibrosis, noting that ruxolitinib’s short half-life necessitates twice-daily dosing, which may reduce adherence. Vaughn highlights that an extended-release formulation, enabling once-daily dosing, may improve adherence, maintain disease control, and lessen cytopenias.

This educational resource is independently supported by Incyte. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.

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In this interview, Kiladjian explores the impact and multifactorial causes of myelofibrosis-related anemia, with particular attention to the on-target effects of JAK inhibition. He reviews currently approved JAK inhibitors, emphasizing the anemia benefits seen with momelotinib and pacritinib. Kiladjian also underscores that JAK inhibitors alone do not completely address myelofibrosis-related anemia, highlighting the potential of JAK inhibitor-based combination therapies to address this unmet need.

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In this interview, Mascarenhas explores the emerging strategies for myelofibrosis-associated anemia, with a focus on agents targeting the TGF-β superfamily members and hepcidin modulation, including luspatercept, elritercept, and DISC-0974. Mascarenhas notes that whether these approaches are most effective as single agents, in combination, or at specific stages of anemia progression remains to be determined. 

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During this interview, Gerds discussed the burden and management of myelofibrosis-associated anemia. He explained its prevalence, prognostic importance, and multifactorial causes. Gerds also reviewed currently available therapies, combination strategies, and the need for further disease-modifying approaches.

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Passamonti provides an overview of the mechanism of action of PIM1 kinase inhibitors. He then discusses results from a phase I/II trial of nuvisertib, a first-in-class selective PIM1 kinase inhibitor, in patients with R/R MF.  

This educational resource is independently supported by Sumitomo Pharma. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.   

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This educational resource is independently supported by GSK and Bristol Myers Squibb. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource. 

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During the European School of Haematology (ESH) 4th How to Diagnose and Treat: CML/MPN conference, the MPN Hub hosted a symposium titled “Anemia in myelofibrosis: Sequencing therapies to optimize patient outcomes.”

The symposium closed with a panel Q&A session with live audience participation. The panelists, Jean-Jacques Kiladjian, Francesco Passamonti, and Paola Guglielmelli, shared their perspectives on the optimal sequencing of therapies for patients with myelofibrosis-related anemia, the use of iron chelation therapy, potential future combination therapies, and the use of anemia supportive agents.

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During the European School of Haematalogy (ESH) 4th How to Diagnose and Treat CML/MPN conference, the MPN hub held a symposium on March 9, 2025, titled, Anemia in myelofibrosis: Sequencing therapies to optimize patient outcomes. Here, we share a presentation by Paola Guglielmelli, University of Florence, Florence, IT​, discussing the optimal sequencing of therapies in patients with myelofibrosis and anemia.

Guglielmelli discussed the differences between myeloproliferative and cytopenic myelofibrosis (MF), highlighting the limited treatment options in patients with severe cytopenias. She discussed the British Society of Haematology and National Comprehensive Cancer Network guidelines for the treatment of anemia in patients with MF, which both suggest the use of momelotinib in patients with MF and anemia and symptomatic splenomegaly.

Guglielmelli then presented three patient cases and discussed the clinical evidence that influences treatment decisions specific to each case.

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During the European School of Haematalogy (ESH) 4th How to Diagnose and Treat CML/MPN conference, the MPN Hub held a symposium on March 9, 2025, titled Anemia in myelofibrosis: Sequencing therapies to optimize patient outcomes. Here, we share a presentation by Francesco Passamonti, Università degli Studi di Milano, Milan, IT, discussing the treatment landscape for patients with myelofibrosis and anemia.

Firstly, Passamonti provided an overview of current treatment strategies for patients with myelofibrosis-related anemia, including red blood cell transfusion, erythropoiesis-stimulating agents, androgens, splenectomy, immunomodulatory drug agents, and Janus kinase inhibitors. He then discussed key efficacy and safety data from phase III trials of ruxolitinib, fedratinib, pacritinib, and momelotinib, with a focus on anemia.

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During an MPN Hub symposium presented at the European School of Haematology (ESH) 4th How to Diagnose and Treat: CML/MPN conference, MPN Hub steering committee Chair Jean-Jacques Kiladjian, Université Paris Cité and Hôpital Saint-Louis, Paris, FR, presented a review of anemia in myelofibrosis (MF), with a focus on the impact of anemia on patient outcomes.

Key points 

• MF is associated with a range of clinical manifestations and constitutional symptoms, including anemia, that significantly impact patient outcomes.  
• The cause of anemia in MF is multifactorial, including splenomegaly-induced hemodilution and increases in plasma volume, red blood cell sequestration and destruction, and ineffective erythropoiesis; it can also be caused or exacerbated by certain MF treatments. 
• Anemia is prevalent in patients with MF, with ~40% of patients anemic at diagnosis and ~25% of patients transfusion dependent at diagnosis, rising to almost 60% and 50% respectively within the first year of diagnosis and increasing further over time. It is often severe (defined as <8g/dL hemoglobin or transfusion dependence). 
• Anemia is included in all MF prognostic scoring systems, and both anemia severity and transfusion dependence are strongly predictive of reduced QoL and survival outcomes in patients with anemia. 

- Anemia and increasing severity of anemia significantly reduce OS for patients with MF.  

- The median OS in transfusion-independent patients is ~62 months, and only ~22 months in highly transfusion-dependent patients. 

- Transfusion burden can impact employment and social life. 

• Improving anemia is an important goal alongside targeting spleen size and symptoms for improving everyday QoL and long-term outcomes in patients with MF. 

- Anemia therefore represents an important consideration for treatment decision-making. 

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Key points

1. Anemia in patients with MF is a complex, multifactorial process, and can be exacerbated by treatment with some Janus kinase inhibitors, including ruxolitinib and fedratinib.
2. Anemia is common in patients with primary MF, with one study reporting hemoglobin levels <10 g/dL in 38% of patients at the time of diagnosis, increasing to 58% in patients seen within 1 year since diagnosis.
3. Anemia can negatively impact overall survival; in a study of 1,109 consecutive patients with primary MF, the median overall survival among patients with no, mild, moderate, and severe anemia was 7.9 years, 4.9 years, 3.4 years, and 2.1 years, respectively.
4. Anemia also negatively impacts patients' quality of life; a study of 85 patients with MF showed that anemia responders had greater improvements in quality of life vs nonresponders.
5. There is a need for effective treatments to address MF-related anemia.

This educational resource is independently supported by GSK and Bristol Myers Squibb. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.

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Gerds highlights the impact of anemia on survival outcomes in patients with MF, and reviews key data from the phase II ACE-536-MF-001 trial (NCT03194542) evaluating the safety and efficacy of luspatercept in patients with MF and anemia, including patients with and without transfusion dependence and concurrent Janus kinase (JAK) inhibition. He then highlights the ongoing randomized, phase III INDEPENDENCE trial (NCT04717414) assessing the safety and efficacy of luspatercept in combination with ruxolitinib in transfusion-dependent patients with MF. Finally, Gerds discusses potential future combinations of luspatercept with ACVR1 inhibitors. 

This educational resource is independently supported by Bristol Myers Squibb. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.

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Aaron Gerds opens by discussing the prevalence and issue of anemia in patients with MF, noting that almost all patients will become anemic at some point in the course of their disease. Gerds discusses luspatercept as a treatment option in this indication, sharing the latest clinical trial data and emphasizing the benefit of a reduction in transfusion dependency for patients treated with luspatercept. The interview closes with a look to ongoing clinical trials, including the INDEPENDENCE study and the implications of these data on future management strategies for anemic myelofibrosis.

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Al-Ali provides an overview of how to improve treatment and outcomes for patients with polycythemia vera, opening with a discussion of the latest advancements in the field and key areas for improvement. Al-Ali shares insights on symptoms management, risk stratification, and the potential applications for machine learning and artificial intelligence in MPN. This interview concludes with a discussion of the goals for treatment and how these may vary between patients and physicians, highlighting the importance of the patient voice in the treatment of MPN.

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Patel opens by highlighting the need for more long-term effective MF treatments and presents long-term data on the cessation of existing therapies such as ruxolitinib. Michaelis and Patel then discuss factors that influence the decision to refer to a clinical trial in patients with newly diagnosed MF; outlining anemia and other symptoms as indicators for referral. They also discuss add-on clinical trials as options for patients who do not achieving optimal response with their current standard of care treatment.

The podcast concludes with a discussion on clinical trial referral versus transplantation in patients not achieving an optimal treatment response with standard of care. Finally, the importance of communicating effectively with the patient and considering their comorbidities is highlighted.

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In this podcast, Michaelis and Patel discuss the factors which determine whether standard of care treatment or referral to a clinical trial is the most appropriate course of action. Patel begins by outlining drugs currently under clinical trial for essential thrombocytopenia and polycythemia vera.  Michaelis and Patel then consider the importance of aligning trial endpoints with the individualized treatment goals of patients. They conclude by discussing how the progression of a patient to second-line therapy, as well as cytogenetic abnormalities that indicate more aggressive disease progression, may underly the decision to consider clinical trials that align with a patient’s goals.

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In this podcast, Michaelis and Harrison discuss the best practices in MPN, in particular in regards to diagnosis. They also discuss the new data that was presented at ASH 2021, such as the MOMENTUM (NCT04173494) study and momelotinib.  

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Currently, patients with PV require frequent phlebotomy. Kremyanskaya discusses promising results from a phase II clinical trial evaluating the safety and efficacy of PTG-300, a novel hepcidin-mimetic, in patients with PV who received three or more phlebotomies up to 6 months before treatment. Kremyanskaya highlights that the need for phlebotomy was eliminated in patients treated with PTG-300. In addition, PTG-300 was well tolerated.

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In this podcast, Jyoti Nangalia reports results from a study using next-generation sequencing to trace acquired MPN mutations in hematopoietic stem cells taken from patients with varying stages of disease presentation. Nangalia discusses unexpected results, such as the acquisition of key driver mutations (JAK2 and DNMT3A) very early in life. She also discusses results observing a variation in the growth rate of cancer cell clones between patients, as well as the correlation of growth rate with disease presentation. Nangalia concludes with possible future applications of these methods in the early detection and prevention of MPN. 

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Results from several studies have shown that interferon alpha is able to induce high rates of complete hematological remission in patients with polycythemia vera, but what are the outcomes in patients who had received interferon alpha and then discontinued treatment?

Kiladjian reports the results of a study comparing the clinical outcome of patients with myeloproliferative neoplasms who discontinued therapy after at least three months of interferon alpha treatment to patients who continued interferon alpha treatment despite achieving a complete hematological remission.

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PV is a disease associated with shorter survival due to short-term complications, such as thrombosis, and long-term complications of progression to myelofibrosis and transformation to acute leukemia, which are associated with poor prognosis. The current treatment guidelines for PV recommend phlebotomy only for low-risk patients and, for a long time, these guidelines favored hydroxyurea over interferon alfa for the initial treatment of high-risk patients.

In this podcast, Abu-Zeinah shares the key findings of a retrospective study comparing myelofibrosis-free survival and overall survival of 470 patients with PV treated with recombinant interferon alfa, hydroxyurea, or phlebotomy only.

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In this podcast, Tiziano Barbui starts by giving some background to the COVID-19 pandemic in Europe. Prof. Barbui has focused on how to help his patients with myeloproliferative neoplasms (MPN) during the outbreak. As a member of the European LeukemiaNet Working party on MPN, Prof. Barbui launched a study in 38 European centers, collecting 180 patients with both MPN and COVID-19. Laura Michaelis asks, are patients with MPN more susceptible to COVID-19 infection? Prof. Barbui discusses this question with reference the prevalence of people infected with COVID-19, who are asymptomatic but show serum-positivity.

Then, Prof. Michaelis asks what the fatality rate was in patients with MPN who also contracted COVID-19. Tiziano Barbui speaks about the results that he found in his hospital and in the study he commissioned. Laura Michaelis highlights that the stage of the epidemic also impacts on case fatality. They go on to comment on the type of comorbidities present in patients with MPN and how this effects their risk of severe disease with COVID-19. This leads to a discussion of the important variables identified during analysis of the data from Prof. Barbui's study. Prof. Michaelis in particular asks about how ruxolitinib modifies the risk for patients with MPN. Tiziano Barbui answers this, paying particular attention to the inflammatory environment in patients with COVID-19.

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In this podcast, Dr Davar starts by providing a background on the importance of the microbiome in adaptive and innate immunity, while Dr Spencer states the importance of the cross-talk between the microbiome and immune system through microbial products, peptides, and metabolites. Dr Davar then explains the concept of immunosurveillance, immunoediting, and checkpoint inhibitors. Dr Spencer describes fecal microbiome transplant studies that showed features of the microbiome can predict response to immunotherapy and effect T-cell expression. Dr Davar then describes some of the studies that are looking at fecal microbiome transplant in combination with checkpoint inhibitors. He goes on to discuss studies investigating the use of live bacterial products to elicit the same effects as fecal microbiome transplant, particularly the mediation of CD8 T cells. Dr Spencer also talks about probiotics, antibiotics, and diet and explains how this can affect the gut microbiome and describes studies looking at these features in terms of response to immunotherapies. She also describes the microbiome research related to graft-versus-host-disease and the impact of higher alpha diversity on post-transplant survival, while Dr Davar explains how the microbiome may also affect toxicity and side-effects of cancer immunotherapies. 

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