JAK Inhibitors Reduce Thromboembolic Risk in Myeloproliferative Neoplasm Therapy

Posted on by

March 11, 2025

Author(s): Alex Biese

Fact checked by: Ryan Scott

Treatment with Janus kinase inhibitors (JAKis) has been found to be associated with a reduction in risk of thromboembolic events among patients with myeloproliferative neoplasms (MPNs), according to research findings.

These findings were published in eJHaem, and are driven by observations of treatment with Jakafi (ruxolitinib) for patients with polycythemia vera and myelofibrosis, researchers noted.

“In this meta-analysis, JAKi [used for] MPN [treatment] was associated with a reduced risk of thromboembolic events compared [with] control, primarily driven by studies of [Jakafi] in polycythemia vera and myelofibrosis,” first study author Roberta Dunn and colleagues wrote in the study. “JAKi treatment was not associated with an increased risk of [major adverse cardiovascular events] or hypertension, adding to the existing body of evidence demonstrating the safety of JAKi in the treatment of MPNs. Further prospective clinical trials are warranted to confirm these findings and characterize the cardiovascular profile of other JAKis in all types of MPNs.”

Dunn is a medical student at the School of Medical Education, King’s College London, as well as a student researcher at Guy’s and St Thomas’ NHS Foundation Trust, in the United Kingdom.

MPNs, according to the Cleveland Clinic, are rare blood cancers that involve the patient’s body making too many red blood cells, white blood cells or platelets. JAKis, as explained by the National Cancer Institute, block the actions of enzymes which control cell signaling and growth, the number of blood cells and platelets made in the bone marrow, inflammation, and immune cell activity. Blocking these enzymes may help prevent abnormal blood cells or cancer cells from growing.

Read more

Promising New Treatment for Myelofibrosis Blood Cancer Using a Combination Targeted Therapy 

Posted on by

By Julie Grisham

An international phase 3 clinical trial of a new drug combination for treating the blood cancer myelofibrosis found that adding a second, experimental drug to standard treatment was more effective than the standard treatment alone. Further, adding the second drug did not significantly increase side effects. Memorial Sloan Kettering Cancer Center (MSK) enrolled the most patients in the trial.

“This is one of the largest myelofibrosis clinical trials to date,” says MSK leukemia specialist Raajit Rampal, MD, PhD, lead author of the study, published March 10 in Nature Medicine. “There is a real unmet need for patients with this disease, and the findings from this trial represent an exciting advance.”

This study looked at adding an experimental drug called pelebresib to the drug ruxolitinib (Jakafi®), which is the current treatment for myelofibrosis. Both drugs are targeted therapies. Pelebrisib blocks the action of proteins involved in inflammation and cancer; ruxolitinib blocks a protein called JAK. This combination approach was based on ongoing research from the lab of MSK leukemia specialist and physician-scientist Ross Levine, MD.

Read more

A Toolkit for Healthcare Transition for Adolescents With Classical Myeloproliferative Neoplasms

Posted on by

March 2025

Nicole Kucine1, Holger Cario2, Ghaith Abu-Zeinah1, Maria Caterina Putti3, Nicolas Boissel4, Maria Luigi Randi3, Linda Resar5, Martin Griesshammer6, Jean-Jacques Kiladjian4

Abstract

Classical myeloproliferative neoplasms (MPNs) are being identified more frequently in adolescents. There is no guidance on the healthcare transition of young MPN patients from pediatric to adult medicine. Therefore, we convened an international panel of experts in both pediatric and adult MPN care to develop three tools to facilitate high-quality healthcare transition: a physician education tool, a transition readiness assessment tool, and a consensus statement of practice recommendations to ensure a more seamless transition in the care adolescents receive. These tools can help ensure a better healthcare transition for young patients. The next steps include evaluating the readiness assessment tool with adolescent patients.

Read more

The role of psychosocial adjustment in the quality of life of patients with myeloproliferative neoplasms

Posted on by

March 7, 2025

A.A.M. Eppingbroek, L. Lechner, E.C. Bakker, M.D. Niijkamp, M.A. de Witte, C.A.W. Bolman

Abstract

Purpose

Myeloproliferative neoplasms (MPNs) can cause a high symptom burden that negatively affects quality of life (QoL). The way patients deal with their disease and how this impacts their QoL is important to understand, yet virtually unknown. The aim of this study is to investigate whether and how psychosocial adjustment affects QoL in MPN patients.

Methods

A longitudinal study was conducted in 338 MPN patients to investigate whether and how baseline measurements of psychosocial adjustment could predict QoL outcomes six months later. Psychosocial adjustment to illness was operationalized by: coping, self-management, resilience and illness identity (II). We tested the hypotheses that high scores on respectively problem-solving coping, self-management, resilience, II-subscales acceptance and enrichment, and low scores on II-subscales rejection and engulfment are associated with high scores on QoL. We performed a multiple hierarchical regression analysis including sociodemographic and disease-related variables and baseline QoL as control variables.

Results

II-subscale engulfment had the most pronounced negative impact on QoL (β.47, p<.001). After the introduction of the control variables, the effect of engulfment remained statistically significant (β.16, p<.01). Additionally, baseline QoL (β.32, p<.001), treatment option wait-and-see (β.11, p<.05), and MPN symptom burden at T2 (β.36, p<.001) demonstrated significance. The other variables measuring psychosocial adjustment did not relate significantly to QoL.

Conclusion

The findings of this study illustrate the significant adverse effect of engulfment on patients’ QoL, underscoring the importance of providing psychosocial guidance to mitigate the patients’ feelings of being overwhelmed by the disease.

New MF Study Recruiting Participants for Its Phase 3 Portion

Posted on by
Özge Özkaya, MSc, PhD
Publish Date

A phase 1/3 clinical trial testing the safety and efficacy of selinexor plus ruxolitinib in patients with myelofibrosis (MF) who are Janus kinase (JAK) inhibitor-naïve is now recruiting participants for its phase 3 portion.

The global, multicenter, 2-part study aims to recruit an estimated 350 participants with MF. Participants were all at least 18 years of age.

The study consists of an experimental phase 1a, experimental phase 1b, and experimental phase 3 portion.

In the experimental phase 1a portion, 1 group of patients were given 40 mg of oral selinexor once a week on days 1, 8, 15, and 22 of each 28-day cycle together with 15 or 20 mg of ruxolitinib twice a day based on their platelet count at baseline while another group was given 60 mg of oral selinexor on the same days and the same dose of ruxolitinib as the first group.

In the experimental phase 1b, patients were given either 40 or 60 mg of oral selinexor once a week on days 1, 8, 15, and 22 of each 28-day cycle and the same dose of ruxolitinib.

In the experimental phase 3 portion, patients will either be given a fixed starting dose of 60 mg of oral selinexor or a placebo once a week on days 1, 8, 15, and 22 of each 28-day cycle together with the same dose of ruxolitinib.

The primary outcome measures of the phase 1 portion of the trial was the maximum tolerated dose and recommended phase 2 dose of selinexor and the number of participants with adverse events by severity, nature, and occurrence.

Read more

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

Posted on by

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.

Read more

Patients With MF May Benefit From Interdisciplinary Care and Personalized Treatment

Posted on by
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.

Read more

What to Know About Myeloproliferative Disorders Clinical Trials

Posted on by

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.

Read more

Managing Polycythemia Vera to Reduce Risks and Improve Lives

Posted on by

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.

Read more

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

Posted on by

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.

Read more