Tag Archives: myeloproliferative neoplasms

MOMENTUM Trial Outcomes: Guiding Therapy for Myelofibrosis With Anemia and Splenomegaly

Posted on by

By Pankit Vachhani, MD
Edward Pearson, MD
elists 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.

Summary of MOMENTUM Trial: Momelotinib in Anemic, Symptomatic Myelofibrosis

Study Design and Population

  • Patient characteristics:
    • Required hemoglobin <10 g/dL
    • Symptomatic disease
    • Previously treated with Janus kinase (JAK) inhibitor therapy
  • Design elements:
    • Primary end point was symptom-driven
    • Active comparator arm (danazol) rather than placebo
    • Included a washout period (unlike SIMPLIFY-2)

Key Findings

  • Primary end point:
    • Momelotinib demonstrated superior symptom benefits compared to danazol
  • Secondary end points:
    • Multiple secondary end points met with superiority
    • Stronger spleen volume reduction data (SVR25, SVR35) than in SIMPLIFY-2
    • Confirmed anemia benefits

Clinical Implications

  • Comprehensive benefit profile:
    • Triple benefit: spleen reduction, symptom improvement, and anemia benefits
    • Washout period may have contributed to clearer demonstration of spleen benefits compared to SIMPLIFY-2
  • Clinician perspective:
    • Some practitioners noted less direct relevance of danazol comparison in their practice
    • Nevertheless, provided further evidence of momelotinib’s anemia benefit
    • Results support momelotinib use in patients with anemic, symptomatic myelofibrosis who have received prior JAK inhibitor therapy

The MOMENTUM trial reinforces momelotinib’s position in the treatment algorithm, particularly for patients with anemia who have been previously treated with other JAK inhibitors.

Read more

Strategic JAK Inhibitor Sequencing: Translating SIMPLIFY I/II Outcomes to Optimize Myelofibrosis Management

Posted on by

By Pankit Vachhani, MD
Edward Pearson, MD

Summary of Momelotinib Clinical Trials and Second-Line Applications

SIMPLIFY-1 (First-Line Setting)

  • Efficacy comparison with ruxolitinib in newly diagnosed myelofibrosis:
    • Spleen response: Momelotinib demonstrated spleen volume reduction
    • Symptom improvement: Not as robust as ruxolitinib
    • Anemia benefit: Preserved transfusion independence at week 24 vs baseline, while ruxolitinib showed slight decline
  • Clinical considerations for newly diagnosed myelofibrosis with moderate anemia:
    • Potential benefit of single-agent therapy (avoiding combination with erythropoiesis-stimulating agents)
    • When anemia contributes significantly to symptom burden, momelotinib may be preferable

SIMPLIFY-2 (Second-Line Setting)

  • Study design: Effectively a comparison of momelotinib vs ruxolitinib in previously treated patients
    • No washout period between treatments
  • Key outcomes:
    • Spleen response: Comparable between momelotinib and control (“a wash”)
    • Anemia: Clear advantage for momelotinib
    • Symptom control: Superior with momelotinib in the second-line setting
  • Expert opinion on optimal positioning:
    • Panel indicated greater preference for momelotinib in the second-line setting
    • Particularly valuable in patients with worsening anemia or diminishing spleen response on ruxolitinib
    • Setting appropriate expectations is crucial; emphasize anemia and symptom benefits rather than additional spleen reduction

Read more

Pegylated Interferons: Still a Major Player for the Treatment of Myeloproliferative Neoplasms

Posted on by

Michael Daunov, DO1 and Rebecca B. Klisovic, MD1

Overview

Over the past 35 years, interferons have been explored in various formulations for the management of Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs), such as essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis, and remain a key tool in caring for patients with these diseases. These agents are excellent cytoreductive agents with high rates of hematologic response, are helpful in symptom management, and have a long track record of safety and manageable toxicities. More recently, they have shown promise in sustaining responses over many years, with associated reductions in driver mutations (JAK2, MPL, CALR) of these diseases, particularly in PV and ET. Since reductions in molecular mutant allele burden have been correlated with several response outcomes such as reductions in both thrombotic risk and disease progression, there is emerging proof that interferons may offer disease-modifying activity. These long-term benefits and their use as the preferred agent in young pregnant women who need cytoreduction make interferons often the first choice in young adult population who harbor a lifetime risk of progression. Looking forward, the prospect of sustained treatment-free responses, like chronic myeloid leukemia after deep molecular response, and normal life expectancy may also be on the frontier. Despite relative rookies such as JAK inhibitors in the MPN landscape, the veteran in the game, interferon, remains a key player.

Read more

National Health Expenditure Associated With Myeloid Neoplasms Survival in Europe

Posted on by
Andrea S. Blevins Primeau, PhD, MBA
Publish Date

An analysis of the EUROCARE found that lower total national health expenditure (TNHE) was associated with shorter survival among patients with some types of myeloid neoplasms (MNs), according to a report published in the European Journal of Oncology.

The researchers also reported that 10-year relative excess risk of death (RER) was generally higher for patients in regions with lower TNHE.

EUROCARE-6 is a dataset in the EUROCARE study that is derived from 27 European countries of patients aged 15 or older diagnosed with an MN between 2001 and 2013. MNs included acute myeloid leukemia (AML), myeloproliferative neoplasms (MPNs), chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and myelodysplastic syndrome (MDS).

There were a total of 267,968 MN cases in the dataset, of which, 41.1% were AML, 32.2% were MPNs, 11.7% were CML, 6.8% were PV, 7.4% were ET, and 19.6% were MDS, and 4.4% were MDS/MPN.

Countries in the lowest TNHE quartile included Bulgaria, Croatia, Estonia, Latvia, Lithuania, Poland, and Slovakia. Countries in the highest TNHE quartile included Austria, Denmark, Germany, Norway, and Switzerland. The median follow-up was 13 years.

At 10 years, the age-standardized relative survival (ASRS) ranged from 61.2% for MPNs to 15.6% for AML. Within MPNs, the 10-year ASRS was 75.2% for ET, 70.9% for PV, and 52.5% for CML.

Countries in the lowest TNHE quartile demonstrated lower 10-year ASRS rates compared with countries in the highest quartile for AML, MPN, and MDS.

A similar trend was observed for 10-year RERs for most MNs, with higher RERs associated with lower TNHE quartile. For example, the lowest TNHE quartile was significantly associated with a greater 10-year RER for MPN (RER, 1.32; 95% CI, 1.30-1.35), AML (RER, 1.28; 95% CI, 1.25-1.31), and acute promyelocytic leukemia (RER, 1.42; 95% CI, 1.12-1.80).

The highest quartile was significantly associated with lower 10-year RER for MPN (RER, 0.80; 95% CI, 0.78-0.81) and AML (0.86; 95% CI, 0.84-0.88), but not some subtypes of AML and APL.

“TNHE is associated with geographical inequalities in MN prognosis,” the researchers concluded in their report. “Policy decisions on allocating economic resources are needed to reduce these differences.”

Read more

Biomed Valley Discoveries Announces First Patient Dosed in Phase 1/2 Combination Study of Ulixertinib with Ruxolitinib (Jakafi®) in Patients with Myelofibrosis

Posted on by

Provided by GlobeNewswire  

— Dual targeting of JAK 1/2 (ruxolitinib) and ERK 1/2 (ulixertinib) may represent a novel treatment approach for myelofibrosis and possibly other myeloproliferative neoplasms

KANSAS CITY, Mo., April 28, 2025 (GLOBE NEWSWIRE) — Biomed Valley Discoveries (BVD), a clinical-stage biotechnology company guided by its founders’ intent of bringing hope for life to patients, today announced that the first patient has been dosed in a Phase 1/2 combination study of ulixertinib, BVD’s highly selective, first-in-class ERK 1/2 inhibitor with ruxolitinib, a JAK1/JAK2 inhibitor for the treatment of myelofibrosis, a rare type of bone marrow cancer that disrupts the body’s normal production of blood cells.

Raajit Rampal, M.D., Ph.D., a hematologist-oncologist with Memorial Sloan Kettering Cancer Center who specializes in the treatment of myeloproliferative neoplasms and leukemia, is the lead principal investigator for this investigator-initiated trial.

“We’re thrilled to announce the milestone of first patient dosed in this trial, and grateful for the opportunity to collaborate with Dr. Rampal and Incyte to explore the potential of ERK inhibition as a complement to JAK inhibition for the treatment of patients with myelofibrosis,” said Brent Kreider, Ph.D., President of BVD. “This trial helps further our commitment to fully interrogate the potential of direct ERK inhibition to address unmet patient needs in various cancer settings where MAPK signaling is implicated.”

Read more

Diagnosis and Management of PV and ET in Pediatric Populations Needs Improvement

Posted on by
Caleb Rans, PharmD
Publish Date

Polycythemia vera (PV) and essential thrombocythemia (ET) are rarely diagnosed in children, adolescents, and young adults. As the median age at diagnosis for these conditions is usually over 60 years, few pediatricians are familiar with their clinical, biological, and genetic features.1-3 Early diagnosis is essential to assess the need for specialized treatments and to prevent long-term complications, such as hemorrhage, thrombosis, or progression to secondary malignancies.1

In a 2-part study published in the European Journal of Pediatrics, Agathe Picard, MD, of the department of pediatric oncohematology at the Rennes University Hospital in France, and colleagues, analyzed practices around the diagnosis and management of pediatric patients with PV and ET in France.

Methodology and Study Design

In the first part of the study, a national practice survey about pediatric patients diagnosed with PV or ET was performed. The 8-question survey was sent to all pediatrician members of the leukemia committee of Société Française de lutte contre les Cancers et leucémies de l’Enfant et de l’adolescent (SFCE), and all hematologist members of France Intergroupe des Syndromes Myéloprolifératifs (FIM).

AYA [patients] should be referred to specialized units that consider the social, psychological, and educational needs of these patients.

In the second part, a retrospective cohort study was conducted at 7 pediatric oncohematology departments in western France. The researchers analyzed clinical, biological, and genetic data, as well as treatment and complication patterns from 17 pediatric patients with PV or ET, all of whom were diagnosed before the age of 18.

Read more

Working to Address Unmet Medical Needs in MPNs

Posted on by

April 24, 2025

Author(s): John Crispino

Fact checked by: Alex Biese, Spencer Feldman

In his research into myeloproliferative neoplasms, or MPNs, John Crispino is focused on a couple of key areas when it comes to understanding the underlying biology of the disease, as he explained in an interview with CURE.

Crispino is the director of the division of experimental hematology at St. Jude Children’s Research Hospital in Memphis, Tennessee, where he is also the Wall Street Committee Endowed Chair and principal investigator of the Crispino Lab. The Crispino Lab, according to its website, is focused primarily on myeloid cells, centered on the mechanisms of normal and abnormal cell development.

“There are two major areas that we study,” Crispino told CURE. “The first is the biology of megakaryocytes. Those are the cells that make platelets. … The second major area of research is on leukemic progression. So I would say that that progression to acute leukemia is really terrible outcome for patients, and we have very few therapies for patients that do advance at that stage. So our research in the past few years has focused on understanding the mechanism.”

Crispino sat down recently with CURE to discuss his research.

Read more

 

Protein Disulfide Isomerase Could Be Therapeutic Target for MF

Posted on by
Özge Özkaya, MSc, PhD
Publish Date

Protein disulfide isomerase may be involved in the underlying pathogenesis of thrombotic events in Philadelphia-negative myeloproliferative neoplasms such as myelofibrosis (MF), according to a new study published in the Egyptian Journal of Internal Medicine.

It could also be valuable in predicting the risk of developing thromboembolic events, the researchers noted.

These findings suggest that protein disulfide isomerase could be used as a therapeutic target to prevent thrombotic events in patients with MF and other myeloproliferative neoplasms.

For the study, a team of researchers, led by Mai Galal Elshenoufy, MD, PhD, from Cairo University in Egypt, measured the levels of protein disulfide isomerase in the serum of patients with myeloproliferative neoplasms and assessed its role as a possible marker of increased risk of thromboembolic events.

They found that the levels of the enzyme were pathologically high in the serum of patients with myeloproliferative neoplasms compared to controls. The levels were also higher in patients with arterial thrombosis, but this finding had no statistical significance.

Future work should evaluate the levels of protein disulfide isomerase in a larger group of patients with myeloproliferative neoplasm with and without thrombotic events, and in patients with arterial versus venous thrombosis, they said.

Finally, measuring the levels of protein disulfide isomerase before and after aspirin therapy could give clues about the effect of this treatment, they added.

Read more

Clinical Trials Can Open Doors for Patients With Myeloproliferative Neoplasms

Posted on by

By Kathryn Johnson, DNP, MSc, FNP-BC
Fact checked by Bridget Hoyt

Educating patients on the “risks and benefits” of clinical trials is a part of the pipeline for better treatment options in myeloproliferative neoplasms (MPNs) in which nurses can engage, said a nurse practitioner.

For patients with MPNs, clinical trials have paved the way for better treatment outcomes, increasing options vastly within a short amount of time. In an interview with Oncology Nursing News, Kathryn Johnson, DNP, MSc, FNP-BC, spoke to the importance of the development of these options and nurses’ role in making those possible.

As Johnson, a clinical program manager at Icahn School of Medicine at Mount Sinai New York, outlined, nurses can play a key part in informing patients on what to expect on clinical trials. She advised not only being prepared with information patients should know, but making time for patients to air their concerns and ask questions as well.

Johnson added that in the time that she has been working in oncology, multiple advancements have been made in the treatment of MPNs. She expects this trend to continue in the coming years.

Read more

Thrombosis May Increase Risk of Cardiovascular Disease, Secondary Cancers in Myeloproliferative Neoplasms

Posted on by

April 21, 2025

Sarah Dingli, Saubia Fathima, Priyansh Faldu, Naseema Gangat, David Dingli & Ayalew Tefferi

Primary myelofibrosis (PMF) is a myeloid neoplasm that is currently classified in the category of JAK2 mutation-prevalent myeloproliferative neoplasms (JAK2-MPNs) [1]; other members of JAK2-MPNs include essential thrombocythemia (ET) and polycythemia vera (PV). JAK2-MPNs are characterized molecularly by JAK-STAT activating mutations, involving JAK2, CALR, and MPL genes, and morphologically by trilineage myeloid proliferation in the bone marrow (BM) that is accentuated by megakaryocyte proliferation and atypia [2]. Peripheral blood (PB) manifestations of JAK2-MPNs include leukocytosis, thrombocytosis, and/or erythrocytosis while other disease features include splenomegaly, thrombosis, bleeding, microvascular disturbances, pruritus, and constitutional symptoms. Patients with MPN are at risk for premature death and disease progression into a fibrotic or leukemic disease phase [3]. Disease complications in JAK2-MPNs are most severe in PMF where median survival is estimated at 4.4 years and leukemic progression at 9%, at a median follow-up of 3.2 years [4].

Leukocytosis, in general, has long been identified/suspected as a risk factor for a number of disease complications in JAK2-MPNs including overall and leukemia-free survival [5, 6], disease progression [7, 8], thrombosis risk [9,10,11], and extramedullary hematopoiesis [12]. Considering the multicomponent nature of leukocytes, more recent studies in JAK2-MPNs have appropriately looked into the differential prognostic impact of absolute neutrophil (ANC) [13,14,15], monocyte (AMC) [13, 16,17,18,19], and lymphocyte (ALC) counts [13,14,15]. By comparison, fewer studies have reported on the prognostic contribution of absolute basophil (ABC) or eosinophil (AEC) counts in JAK2-MPNs, in general, and in PMF, in particular, not associated with tyrosine kinase fusion genes [20,21,22,23,24]. On the other hand, the prognostic relevance of basophilia in chronic myeloid leukemia (CML) is well established and is taken under consideration in defining accelerated phase CML [25, 26]. In the current study, we utilized a large Mayo Clinic database of patients with PMF in order to describe the prevalence and the clinical, molecular, and prognostic correlates of ABC and AEC.

Read more