Exploring the interplay between myeloproliferative disorders and atherosclerosis

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Published April 3, 2025

Maham Khan, Sandipta Banerjee, Rekha Kumari, Shubhayu Roy Chowdhury, Nada Madkour, Ikponmwosa Jude Ogieuhi, Chinonyelum Emmanuel Agbo, Victor Oluwatomiwa Ajekiigbe, Olanipekun Lanny Ntukidem, Folajimi Josiah Atunde & Chukwuemelie Darlington Okeke

Abstract

The relationship between hematologic malignancies and atherosclerosis is vital in clinical conditions due to common risk factors. These two diseases may negatively affect cardiovascular health, so understanding their complex dynamics is essential for detecting disease mechanisms and establishing effective patient care. This review aims to focus on the involvement of hematologic malignancies in the onset and progression of atherosclerosis at a biological level. Furthermore, it looks at the case for heightened cardiovascular risk in patients with hematological cancers and the chances of management and treatment against it. A comprehensive literature review was performed, and studies that revealed the link between hematologic malignancies and atherosclerosis were preferred. Inclusion and exclusion criteria guided the selection of studies for consideration. The biological pathways between hematologic malignancies and atherosclerosis have been elucidated, including the inflammatory pathways and the shared risk factors. Clinical evidence reveals that cardiovascular diseases are more likely to occur in patients with hematologic cancers, thus showing the necessity of targeted preemptive measures to lower this risk. The findings reveal that it is essential to consider cardiovascular health when handling hematologic malignancies. Future research should focus on creating holistic treatment procedures that jointly deal with both conditions, which will be necessary to enhance patients’ lives and well-being.

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Navigating the peginterferon Alfa-2a shortage: practical guidance on transitioning patients to ropeginterferon alfa-2b

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Published April 3, 2025

Ruben Mesa, Abdulraheem Yacoub, Tsewang Tashi, Wanxing Chai-Ho, Chang Ho Yoon & John Mascarenhas

Dear Editor,

We write to highlight the critical shortage of peginterferon alfa-2a (peg-IFN), as confirmed by the FDA [1], which has impacted many patients with myeloproliferative neoplasms (MPNs). Those relying on peg-IFN for long-term disease control in polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) face supply disruptions that can compromise disease stability and overall health.

Ropeginterferon alfa-2b (ropeg-IFN) is a viable alternative. It is the only FDA-approved interferon for PV and is considered first-line therapy as per the January 2025 NCCN Guidelines [2]. Though not yet approved for ET or MF, off-label use may be justified in situations where no other options exist. Our group has accumulated experience in transitioning patients from peg-IFN to ropeg-IFN due to historic insurance issues and clinical trial participation, allowing us to propose practical strategies for safe conversion.

A best-practice approach to dose equivalence, based on collective experience and real-world data, is pragmatic given that no formal head-to-head dosing trials exist.[3,4,5] For patients previously on peg-IFN 135–180 µg weekly, we typically initiate ropeg-IFN at 250–350 µg every two weeks, adjusting for hematologic response and tolerability. Those on lower peg-IFN doses (45–90 µg/week) may begin on 200–250 µg every two weeks. If disease control proves challenging, starting at, e.g., 350 µg with possible escalation to 500 µg every two weeks can be considered. Whichever starting dose is chosen, close monitoring and dose adjustments are essential to maintain efficacy while minimizing toxicity.

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Global, regional, and national burden of myelodysplastic syndromes and myeloproliferative neoplasms, 1990-2021: an analysis from the global burden of disease study 2021

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Xinyue Gou 1, Zhuo Chen 2,*, Yudi Shangguan 3

Abstract

Objective

To analyze the trends and cross-country inequalities in the burden of Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) over the past 30 years and forecast potential changes through 2045.

Methods

Estimates and 95% uncertainty intervals (UIs) for incidence, deaths, and disability-adjusted life-years (DALYs) associated with MDS/MPN were obtained from the Global Burden of Diseases (GBD) 2021 database. We described the epidemiology of MDS/MPN at global, regional, and national levels, analyzed trends in the burden of MDS/MPN from 1990 to 2021 through overall, local, and multidimensional perspectives, decomposed the burden based on population size, age structure, and epidemiological changes, quantified cross-country inequalities in MDS/MPN burden using standard health equity methods recommended by the WHO, and predicted changes of MDS/MPN burden to 2045.

Results

The global incidence of MDS/MPN has shown a marked increase, escalating from 171,132 cases in 1990 to 341,017 cases in 2021. Additionally, the burden was found to be significantly greater in men compared to women. The overall global burden of MDS/MPN exhibited a consistent increase from 1990 to 2021, although the growth rate showed a noticeable slowdown between 2018 and 2021. Decomposition analysis identified population growth as a key factor influencing the variations in the burden of MDS/MPN. An inequality analysis across countries indicated that high Socio-demographic Index (SDI) countries bore a disproportionate share of the MDS/MPN burden, with significant SDI-related disparities remaining evident. Interestingly, while the incidence and deaths of MDS/MPN, along with the age-standardized rate (ASR) for DALYs, are projected to decline annually from 2020 to 2045, the absolute number of cases for these indicators is expected to continue rising. By 2045, the projected numbers are estimated to reach 457,320 cases for incidence, 82,047 cases for deaths, and 1,689,518 cases for DALYs.

Conclusions

As a major public health issue, the global burden of MDS/MPN showed an overall increasing trend from 1990 to 2021, which was primarily driven by population growth and aging. The largest share of the MDS/MPN burden was seen primarily in men, with older demographics. Countries with elevated SDI experienced a significantly higher burden of MDS/MPN. While the burden of MDS/MPN was most pronounced in high SDI quintile, the fastest growth was observed in the low-middle SDI quintile, especially in tropical Latin America. This study highlighted great challenges in the control and management of MDS/MPN, including both growing case number and distributive inequalities worldwide. These findings provide valuable insights for developing more effective public health policies and optimizing the allocation of medical resources.

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JAK Inhibitors Associated With Less Thromboembolic Events in MF

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Leonardo Jaimes, MD
Publish Date:

Janus kinase inhibitors (JAKi) therapy could prevent thromboembolic events in patients with myeloproliferative neoplasms (MPNs) such as myelofibrosis (MF), according to a recently published meta-analysis in the Journal of the British Society of Hematology.

Despite the well-documented clinical improvement associated with JAKi therapy in patients with MPNs, adverse effects such as weight gain and cholesterol increase have raised concerns about increased cardiovascular risk. Furthermore, the ORAL surveillance trial demonstrated that JAKi was associated with an increase in the rate of major adverse cardiovascular events (MACEs).

As the effects of JAKi therapy on thrombotic risk are still poorly understood, the authors aimed to compare the rates of MACEs, thrombosis, and hypertension in patients with MPN taking JAKis through a meta-analysis.

The meta-analysis included prospective and retrospective studies involving patients taking JAKi and a JAKi-naive control group. The initial search yielded over 1500 studies, of which 23 met the inclusion criteria.

Nine studies, including over 1800 patients, assessed thromboembolic risk. The pooled analysis with a confidence interval of 95% revealed that the rate of thromboembolic events was 48% lower in patients receiving JAKi therapy. The pooled analysis of the 16  studies analyzing MACE or hypertension, on the other hand, revealed no significant difference between groups.

The authors remarked that the findings correspond with evidence presented by Samuelson et al., which demonstrated that ruxolitinib was associated with lower rates of hemolysis. Furthermore, recent posthoc analysis of the ORAL surveillance trial found that the apparent increased frequency of MACE in patients receiving JAKi therapy was observed in patients with preexisting atherosclerotic disease.

“JAKi treatment was not associated with an increased risk of MACE or hypertension, adding to the existing body of evidence demonstrating the safety of JAKi in the treatment of MPNs,” the authors wrote.

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Mutations With Diagnostic Potential for MF Identified

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Leonardo Jaimes, MD
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Next-generation sequencing (NGS) identified 14 gene mutations with diagnostic and prognostic potential in patients with myelofibrosis (MF), according to a recently published study in the Journal of Applied Genetics.

“The incredible progress that has been made over the last 10 years in the field of genetic diagnostics has prompted the identification of additional genetic abnormalities linked to MPN,” the authors wrote.

Driver mutations in the CALR, JAK2, and MPL genes have a high diagnostic and prognostic value in patients with myeloproliferative neoplasms, like MF. the researchers noted. However, other mutations are also involved in the pathophysiology of these conditions, and many of them are associated with treatment resistance and poorer prognosis, they added.

Therefore, the authors aimed to use an NGS of 40 genes to retrospectively study a cohort of 42 CALR-positive patients with either essential thrombocytosis (ET) or MF and determine the impact of gene mutations in disease progression.

Patients with ET (n=28) and MF (MF) were further divided according to the type of CARL mutation. Among patients with MF, the type 1 CARL mutation represented 92% of the population.

NGS revealed 44 potentially pathogenic variants. The most frequently mutated genes were associated with epigenetic regulatory mechanisms, namely ASXL1, TET2, and DNMT3A. Approximately 48% of patients had additional mutations, 33% had more than one additional mutation, and 23% had high molecular risk mutations.

The presence of additional mutations correlated with disease transformation, as five out of seven patients who progressed from ET to MF had additional mutations. Furthermore, the two patients that progressed to acute myeloid leukemia had additional mutations.

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Reducing Polycythemia Vera–Associated Thrombotic Risk Through Iron Regulation

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April 1, 2025

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

The investigational rusfertide (Takeda), is currently being evaluated in the phase 3 VERIFY trial (NCT05210790) as an injectable therapeutic to treat polycythemia vera (PV) through achieving and sustaining hematocrit control. This agent has already breakthrough therapy, orphan drug, and fast track designations from the FDA.

In part 3 of a discussion, Andrew Kuykendall, MD, clinical researcher at Moffitt Cancer Center and VERIFY investigator, talks of rusfertide’s ability to free patients from being tethered to the need for regular phlebotomies and live a more viable life.

Part 1 and part 2 of this interview are also available to learn more about this potential novel PV treatment.

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Symptom burden in myeloproliferative neoplasms: clinical correlates, dynamics, and survival impact—a study of 784 patients from the Quebec MPN research group

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April 1, 2025

Alisa Poullet, Lambert Busque, Shireen Sirhan, Robert Delage, Ghislain Cournoyer, Ines Chamakhi, Danielle Talbot, Luigina Mollica, Daniele Marceau, Vincent Ethier, Pierre Desjardins, Harold J. Olney, Michaël Harnois & Natasha Szuber

Classic BCR::ABL1-negative myeloproliferative neoplasms (MPN) include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). While patients may benefit from extended survival, they also endure lifelong symptoms, ranging from mild to incapacitating [1]. These include physical manifestations related to hyperviscosity, bone pain, pruritus, constitutional symptoms, and consequences of splenomegaly, among others, as well as psychological symptoms (e.g., depression, anxiety) [2, 3]. Ultimately, symptom burden impairs quality of life (QoL) [4], an independent predictor of mortality [5]. Addressing symptom burden in MPN patients is crucial in guiding and individualizing therapy; however, several important challenges remain, including obscure mechanistic underpinnings and scarcity of robust data to inform practice. While the current patient-reported symptom assessment tool was conceived as a universal instrument for the collective MPN population—facilitating its clinical application, distinct profiles across subtypes may not be captured. Cut-off values determining ‘significant’ scores may also warrant further evaluation. Furthermore, kinetics of symptom profiles over time and correlations with biological variables have not fully been explored. The objectives of the current study were to comprehensively characterize symptom burden in a large MPN cohort, determining: i) age/sex-associated differences; ii) longitudinal dynamics and treatment effects; iii) biologic correlatives; and iv) impact on overall survival (OS) in a real-world population-based setting.

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A Patient Story: Are MPNs Hereditary?

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Our story started when I was heavily pregnant with our first child in July 2022. My husband and I were not aware that he had an MPN. One morning, before he went to the doctor before work where they told him to go to the hospital for potential internal bleeding. He went in and was admitted and spent 2 long weeks where he had numerous CT scans, endoscopies, blood test, and other various medical drips. My husband was released but we still didn’t have answers to what had caused him to have internal bleeding. We were just told they needed to do further tests; however, they were pointing towards something to do with his liver which we were very much confused by.

Time went by and we had our baby girl! We were so busy with the joy of our new arrival we had almost forgotten about the hospital. 4 weeks later we were ablet to finally see a liver specialist with our new baby and were told that he had a blood disorder that caused him to have varices in his throat that burst, causing the internal bleeding. We left the appointment with a sense of relief to finally have an answer.

A few weeks later we had an appointment with the hematologist and were told that he had a JAK2 mutation myeloproliferative neoplasm, a blood cancer. We were devastated by this news. At the age of 31, this was not something we understood or had ever heard of. The only words we heard were “blood cancer” and, even though his hematologist is very knowledgeable and reassuring, we left feeling like our world had been turned upside with a 6-week-old baby girl.

After being told that his MPN diagnosis was not hereditary, we spent numerous hours researching the condition to better understand what we were dealing with. We moved on, so to say, and made the most of every day.

Just before our daughter turned one, we took her into the doctor’s office because she had a cough, and I was worried that she might have enlarged lymph nodes. The doctor didn’t seem too concerned but referred her for some blood tests just to be on the safe side considering my husband’s recent diagnosis. Her test results showed high platelets, and we were told to have the tests repeated as the rise in platelets could have been due to iron deficiency or an infection.

The second blood test once again showed that her platelets were unusually high. The hematologist referred us to genetic testing and another full blood count. Her results came back stating she also had a JAK2 mutation, the same one as my husband’s (JAK2 V617I). After this diagnosis, we sent off nail clipping to confirm that he has a germline mutation.

When our daughter was 6 months old, we became pregnant with our second child. We learned that my mother-in-law also has the JAK2 mutation but hers was never activated. My husband has now been officially diagnosed with polycythemia vera (PV) and is being checked every 6 months with stable blood work. We are now focused on living a positive, happy life despite all the challenges we were presented and remain grateful for our family every day.

 

Optimal Ruxolitinib Dosing in Myelofibrosis Critical for Improved Effectiveness, Survival in Real-World Setting

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March 27, 2025

Author(s): Luke Halpern, Assistant Editor

Patients with myelofibrosis (MF) started on appropriate and highest tolerated doses of ruxolitinib (Jakafii; Incyte Corporation) experienced better trends in response and improved health-related quality of life (HRQoL), highlighting the importance of proper ruxolitinib dosing, timing, and administration to ensure the most effective patient responses in terms of symptom relief, spleen size reduction, and improved overall survival (OS).1

Diagnosis of Myelofibrosis. Laboratory blood bottle (tube), glass slide with blood smear, hematology test, stethoscope lying on notebook with printed text hematological diagnosis

Ruxolitinib is effective at reducing symptoms in myelofibrosis. | Image Credit: © shidlovski – stock.adobe.com

It’s critical for treatment providers administering ruxolitinib for MF to know the expected real-world presentation of treatment complications. Patients being administered ruxolitinib face higher health care resource utilization and clinical burdens, including an increased risk of anemia development and adverse treatment events. Still, the treatment is highly effective when dosed and administered appropriately and when proper consideration of adverse events, such as anemia or graft-versus-host disease, is included in counseling.1,2

According to the investigators, the expected optimal starting dose for initiating ruxolitinib is based on a patient’s baseline platelet count. Further dose titration—up to 25 mg twice daily—can be utilized to maximize efficacy, which has been demonstrated to be dose-dependent. However, suboptimal adherence is consistently reported among patients treated with ruxolitinib, which could contribute to poor survival outcomes and undermine disease control.1,3

Poor adherence rates have been observed in the ongoing Ruxolitinib Observational Study in Myelofibrosis Treated Patients in Italy (ROMEI), an observational study of ruxolitinib-treated patients with MF in Italy. Twenty-four-week findings confirmed ruxolitinib’s therapeutic effects and a favorable safety profile but also indicated that up to one third (25% to 40%) of patients receiving ruxolitinib could have been undertreated despite their clinical presentation necessitating higher doses. An interim analysis, conducted by the current authors, was commissioned to investigate ruxolitinib dosing patterns and correlations with clinical outcomes in patients who completed the first 12 months of follow-up or prematurely discontinued the ROMEI trial.1

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Distress May Be Under-Recognized in Patients With MPN

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March 28, 2025

John Schieszer

Distress is a critical yet underrecognized factor affecting quality of life, treatment adherence, and healthcare utilization in classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs): polycythemia vera (PV), essential thrombocythemia (ET), myelofibrosis (MF), according to results of a retrospective study. The study revealed that despite consensus recommendations, most patients with distress ≥4 were not evaluated by supportive services (SS).

“Our findings underscore the importance of integrating distress screening with actionable follow-ups to ensure that patients receive timely supportive care,” said first study author Rushil V. Patel, MD, an assistant professor of Hematology/Oncology at The University of Alabama at Birmingham. “For hematologists, the key takeaway is that screening alone is insufficient and systematic referral pathways and proactive engagement with supportive services are essential. An interdisciplinary approach could significantly enhance patient-centered care.”

There is an urgent need to address the unmet needs of this population. The National Comprehensive Cancer Network (NCCN) recommends screening patients for distress by a self-reported scale (0-10) and to refer those with scores ≥4 to SS.

Researchers looked at 141 patients (44 PV, 49 ET, and 48 MF). The median age was 63 years (range, 25-89). The researchers retrospectively identified MPN patients at a single center to measure the proportions of patients with distress ≥4 evaluated by an SS (chaplaincy, integrative oncology, palliative medicine, psychiatry, psychology, and social work).

The team also investigated acute care utilization (ACU; ≥1 ED visit or hospitalization) within 6 months of electronic distress screening (EDS). In order to stratify variables associated with distress, the investigators obtained sociodemographic, disease characteristics, and symptom score data. The cohort was predominantly female (62%) and White (77%).

As part of routine care, the NCCN recommends using the MPN-Symptom Assessment Form Total Symptom Score (SAF TSS), which is a validated measure of 10 symptoms clinically relevant to MPNs. Data captured from the EDS included location, time of screening and patient-reported information (gender, race, ethnicity, psychosocial variables). These were linked to the electronic medical record (EMR). Distress was based on a single self-reported question: “How much distress have you been feeling in the past week?”

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