Tag Archives: myeloproliferative neoplasms

Hematologic Cancers Among Patients With Type 2 Diabetes Prescribed GLP-1 Receptor Agonists

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March 6, 2025

Omer S. Ashruf, BS1; Jasmin Hundal, MD, MS, MPH2; Ali Mushtaq, MD3; et al

Introduction

Type 2 diabetes (T2D) and obesity have been identified as independent risk factors for various cancers, including hematologic cancers.1 Glucagon-like peptide–1 receptor agonists (GLP-1RA) have emerged as an effective treatment, offering glycemic control, weight reduction,2 and immune modulation,3 and are associated with lower cancer risk, specifically solid tumors.4 However, the association of GLP-1RA with hematologic cancers remains unexplored. This study aims to compare the risks of hematologic cancers in patients with T2D treated with GLP-1RA compared with metformin and insulin.

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Patients With MF May Benefit From Interdisciplinary Care and Personalized Treatment

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Özge Özkaya, MSc, PhD
Publish Date

A new position paper combining insights from a panel discussion of German experts about the diagnosis and treatment of patients with myelofibrosis (MF) was published in the scientific journal Annals of Hematology. The paper highlights the need for an interdisciplinary approach, adherence to updated World Health Organization (WHO) and the International Consensus Classification (ICC) diagnostic criteria, and personalized treatment approaches for each patient.

The team of authors led by Florian H. Heidel, MD, from the Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation at Hannover Medical School in Hannover, Germany said that by addressing diagnostic challenges and therapeutic nuances, the paper aims to improve outcomes and quality of life for patients in the prefibrotic phase of primary MF.

The panel discussions were grouped under 3 main areas which were:

  • The definition and diagnosis of prefibrotic primary MF, its clinical characteristics, and how they separate from other subentities of myeloproliferative neoplasms.
  • Whether essential thrombocythemia and prefibrotic primary MF are distinguishable entities or part of a continuous spectrum.
  • The therapeutic options and how Janus kinase (JAK)-inhibitor therapy ranks among therapies of prefibrotic primary MF.

The relevant aspects of the panel discussion for each area were then outlined in detail.

It was concluded that profibrotic primary MF has unique morphological, clinical, and molecular characteristics that distinguish it from essential thrombocythemia and overt primary MF and that the diagnostic process relies on the histological analysis of the bone marrow, the identification of genetic mutations, and the exclusion of other myeloid neoplasms.

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What to Know About Myeloproliferative Disorders Clinical Trials

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Medically reviewed by Julie Scott, DNP, ANP-BC, AOCNP — Written by Hope Gillette on March 6, 2025

Myeloproliferative disorders, now referred to as myeloproliferative neoplasms (MPNs), include a group of blood cancers that develop when bone marrow produces too many red blood cells, white blood cells, or platelets.

Some forms of MPNs, such as essential thrombocythemia (ET) respond well to current treatmentTrusted Source, but others, such as primary myelofibrosis, have fewer effective options.

Depending on the specific diagnosis you received, your healthcare team may recommend participating in an MPN clinical trial to expand your treatment possibilities.

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Managing Polycythemia Vera to Reduce Risks and Improve Lives

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March 5, 2025

Author(s): Maggie L. Shaw, Andrew Kuykendall, MD

Polycythemia vera is a classic myeloproliferative neoplasm and a chronic type of leukemia, which often leads to overproduction of various blood cells. Several medications are approved to treat this condition—among them ruxolitinib (Jakafi; Incyte), in December 2014,1 and ropeginterferon alfa-2b-njft (Besremi; PharmaEssentia), in November 20212—and others remain in clinical development. Rusfertide (Takeda) is currently being investigated in the phase 3 VERIFY trial (NCT05210790), with an estimate study complete date of June 2025.3 The hepcidin mimetic has already received breakthrough therapy, orphan drug, and fast track designations from the FDA.

In this interview, Andrew Kuykendall, MD, clinical researcher at Moffitt Cancer Center and a VERIFY investigator, breaks down how polycythemia vera manifests and common ways to reduce its negative impact on patient quality of life while reducing the risk of clinically worsening events.

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Evolution of WHO diagnostic criteria in “Classical Myeloproliferative Neoplasms” compared with the International Consensus Classification

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March 4, 2025

Jürgen Thiele, Hans Michael Kvasnicka, Umberto Gianelli, Daniel A. Arber, Ayalew Tefferi, Alessandro M. Vannucchi, Tiziano Barbui & Attilio Orazi

Abstract

A lively discussion persists regarding the diagnostic criteria for essential thrombocythemia (ET), primary myelofibrosis (PMF) and polycythemia vera (PV), particularly in relation to early/pre-fibrotic myelofibrosis (pre-PMF), a disease entity initially introduced in 2001 by the 3rd edition of the World Health Organization (WHO) classification. The definition and criteria used to diagnose pre-PMF have been progressively modified over time. The most update definition of pre-PMF can be found in the International Consensus Classification (ICC) published in 2022. An updated largely similar definition is also incorporated in the recently published 5th edition of WHO classification (2024). Diagnostic criteria for ET have undergone changes up to 2016/17 for the revised 4th edition of the WHO. In particular the threshold value for platelets were lowered and the important discrimination between “true” and “false” ET (in reality pre-PMF) been widely acknowledged. To avoid misdiagnose in early phase PV, the criteria for gender-adjusted thresholds for hemoglobin/ hematocrit have been lowered and the identification of an appropriate bone marrow (BM) morphology was upgraded as a major diagnostic criterion. Given the prominent role of morphology in MPN-related diagnostic algorithms, the diagnostic adequacy of the BM biopsy (sample procurement and proper laboratory handling) as emphasized in former WHO editions and in the ICC, was not addressed by the WHO 5th. The essential role of genetic markers is recognized by both classifications. A comparison between the revised 4th edition WHO classification and the ICC versus the WHO 5th reveals no significant differences, with the exception of the occurrence of leukoerythroblastosis in pre-PMF considered by the latter as one of the minor diagnostic criteria which seems unwarranted. In contrast to the revised 4th edition, the majority of the microscopic images used for the WHO 5th due to their low magnification and poor technique, do not highlight the diagnosis differences among these entities.

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Genetic Testing Breakthroughs in Blood and Lymph Cancers

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February 28, 2025

Hematopoietic and lymphocytic neoplasms (HLNs) are a diverse group of malignancies affecting blood and lymphatic systems, with outcomes varying from manageable conditions to fatal diseases. Traditional classifications rely on morphology, karyotyping, and fluorescence in situ hybridization (FISH). However, recent advancements in next-generation sequencing (NGS) allow simultaneous genetic profiling of multiple genes, enhancing diagnostic precision and therapeutic strategies. This review examines key molecular applications in diagnosing and managing HLNs, addressing current challenges and proposing solutions to optimize clinical utility.

Chronic Myeloid Leukemia (CML)

CML, historically identified by leukocytosis, is characterized by the BCR::ABL1 fusion gene resulting from the Philadelphia chromosome translocation. This oncogenic fusion drives aberrant tyrosine kinase activity, promoting unchecked proliferation. The introduction of imatinib, a targeted tyrosine kinase inhibitor (TKI), revolutionized CML treatment, leading to normalized white blood cell (WBC) counts within months. However, resistance mutations necessitate molecular monitoring via quantitative PCR, FISH, and karyotyping, ensuring optimal therapeutic adjustments.

Molecular Applications in BCR::ABL1-Negative Myeloid Neoplasms

Certain myeloid neoplasms, such as chronic neutrophilic leukemia (CNL) and chronic eosinophilic leukemia (CEL), lack the BCR::ABL1 fusion gene but exhibit distinct genetic markers like CSF3R mutations in CNL. Classical myeloproliferative neoplasms (MPNs) include polycythemia vera, essential thrombocythemia, and primary myelofibrosis, driven by JAK2, MPL, or CALR mutations. The application of NGS enables comprehensive mutational profiling, aiding accurate diagnosis and prognostication.

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Patients With MF Who Failed Ruxolitinib Treatment May Benefit From Fedratinib

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Özge Özkaya, MSc, PhD
Publish Date

Fedratinib treatment is effective in patients with myelofibrosis (MF) who discontinued ruxolitinib due to treatment failure, according to data from a real-world study published in the scientific journal Future Oncology.

The findings of this study offer a new option for patients with MF whose disease does not respond to ruxolitinib treatment.

To assess the real-world treatment patterns with fedratinib as well as clinical outcomes in patients with primary or secondary MF after ruxolitinib discontinuation, a team of researchers conducted a retrospective, noninterventional medical record review of 196 patients with MF in Germany, Canada, and the United Kingdom.

Data about the patients was provided by 70 physicians of whom 78.6% were primarily hematologists or oncologists.

Of these 196 patients, the majority (76.5%) had primary MF and started treatment with fedratinib at a mean age of 67.7 .

The median duration of treatment with fedratinib was 11.5  months and the median follow-up period was 13.8  months.  Almost half (49.5%) of patients started fedratinib at the dose indicated on the label, i.e. 400  mg per day.

Six months after the start of treatment with fedratinib, 77.7% of patients had symptom response and 66.8% had spleen response.

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Comparison of recognition of symptom burden in MPN between patient- and physician-reported assessment – an intraindividual analysis by the German Study Group for MPN (GSG-MPN)

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Kirsi Manz, Florian H. Heidel, Steffen Koschmieder, Rudolf Schlag, Jörg Lipke, Frank Stegelmann, Martin Griesshammer, Martine Klausmann, Carl Crodel, Andreas Hochhaus, Holger Schulz, Joachim R. Göthert, Haifa Al-Ali, Heiko Becker, Andreas Reiter, Gernot Beutel, Kim Kricheldorf, Tim H. Brümmendorf, Wolfgang Hoffmann, Konstanze Döhner & Susanne Isfort On behalf of the German Study Group for Myeloproliferative Neoplasms (GSG-MPN)

Abstract

Myeloproliferative neoplasms (MPN) are associated with a variety of symptoms that severely impact patients’ quality of life and ability to perform daily activities. Recent studies showed differences in the perception of physician- versus patient-reported symptom burden. However, studies directly comparing patient- and physician-reported ratings are lacking. Here, a retrospective analysis on symptom burden of 3979 MPN patients of the Bioregistry of the German Study Group for MPN was conducted to intra-individually compare physician and patient reports collected at the same time. Cohen’s kappa was calculated to assess the degree of agreement between patient and physician reports. Factors influencing baseline symptom severity were identified using linear regression and adjusted Cox models were calculated to investigate the effect of symptom burden on survival. MPN patients had a high symptom burden, which neither decreased over time nor upon cytoreductive therapy. All symptoms were more frequently reported by patients compared to physicians. Agreement remained low and only slightly improved when considering a higher threshold for patient symptom severity. Patients with severe symptom burden had inferior survival compared to patients with less severe symptoms. Assessment of symptom burden in MPN is therefore insufficient and patient-reported outcome tools need to be implemented into clinical routine.

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Management of Bleeding, Thrombotic and Pregnancy-Related Complications in Women with Myeloproliferative Neoplasms: A Case-Based Review Focusing on Sex-Specific Challenges

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February 25, 2025

by Thita Chiasakul and Ross I. Baker

Abstract

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal hematopoietic disorders that pose unique challenges in women, particularly regarding thrombosis, bleeding, fertility, and pregnancy. Women with MPN exhibit distinct thrombotic and sometimes contradictory bleeding profiles, including a higher prevalence of unusual thrombosis such as cerebral and splanchnic vein thrombosis and increased risk of hemorrhage from anti-thrombotic medication, acquired von Willebrand syndrome and platelet dysfunction. Estrogen-containing contraceptives should generally be avoided due to thrombotic risk. Around 10–20% of newly diagnosed MPN cases are women of childbearing age and the number is increasing annually. MPN patients when compared to controls have a lower rate of live birth rate of 71% vs. 80% with a hazard ratio of 0.78 (95% CI: 0.68–0.90), and increased preterm birth (14% vs. 4%), low birth weight (<2500 g, 10% vs. 4%), and increased cesarean section rate (32% vs. 17%). Management of MPN-related pregnancy requires specific considerations regarding the prevention of thrombosis, bleeding, and pregnancy-related complications. Management strategies during pregnancy include low-dose aspirin and consideration of low-molecular-weight heparin and interferon. Despite these challenges, most women with MPN can achieve successful pregnancies with optimized care. In this case-based review, we present two cases that illustrate key aspects of managing MPN in women, summarize the current literature, and propose a diagnostic and management framework tailored to these complexities.

Fedratinib Shows Safety, Potential as Post-Transplant Therapy in MPNs

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February 21, 2025

Fedratinib (Inrebic) as a maintenance therapy following allogeneic hematopoietic cell transplant given at a 400 mg daily dose was determined to be safe and established as the maximum tolerated dose (MTD) for patients with myeloproliferative neoplasms (MPNs).1 

Findings come from a recent phase 1 trial where experts explored the potential of fedratinib, a JAK2 inhibitor already approved for pre-transplant myelofibrosis, as a post-transplant maintenance therapy to reduce relapse risk and mitigate graft-vs-host disease (GVHD).

In an interview with Targeted OncologyTM, Hany Elmariah, MD, associate member at the Moffitt Cancer Center in the department of bone marrow transplant and cellular immunotherapy, discussed the trial’s findings, the safety profile of fedratinib, and its evolving role in the post-transplant setting.

Targeted Oncology: Could you discuss the background of this study and what motivated the research?

Elmariah: One of my areas of research is transplant for myelofibrosis and myeloproliferative neoplasms. While transplant can be curative, the cure rate, depending on the study, is generally in the 40% to 60% range. The main reason patients are not cured by transplant is largely the risk of relapse, which [occurs when] the cancer returns after the transplant. For those who do not relapse, there is also the risk of toxicity, such as GVHD, where the transplant attacks the patient’s own body. There are many strategies in development, both for myelofibrosis and other cancers, to reduce the risks of relapse and GVHD.

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