Tag Archives: blood cancer

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

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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.

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Introduction to a How I Treat series on myeloproliferative neoplasms

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April 17, 2025

Jason Gotlib, MD

Like other hematologic malignancies, the management of myeloproliferative neoplasms (MPNs) reflects a dynamic assessment of the grades of clinical evidence to guide the appropriateness of therapeutic interventions. The National Comprehensive Cancer Network and European LeukemiaNet have synthesized these data into risk-stratified guidelines to provide foundational approaches for diagnosing and treating MPNs.1,2 However, the biologic, clinical, and molecular heterogeneity of MPNs, as well as the unique treatment goals of individuals often leads to a melding of data-driven algorithms with personalized care approaches informed by shared decision-making between patients and their physicians. Although this hybrid heuristic may introduce some imprecision in this era of precision medicine, it also recognizes that treatment decisions are not completely fated by the results of a multigene next-generation sequencing panel. This is a common theme running through the following 6 articles featured in this How I Treat series on MPNs:

  • Mary Frances McMullin and Claire N. Harrison, “How I treat patients with low-risk polycythemia vera who require cytoreduction”
  • Lucia Masarova and Helen T. Chifotides, “How I individualize selection of JAK inhibitors for patients with myelofibrosis”
  • Akriti G. Jain and Aaron T. Gerds, “How I treat anemia in myelofibrosis”
  • Deepti H. Radia, “How I diagnose and treat systemic mastocytosis with an associated hematologic neoplasm”
  • Andreas Reiter, Georgia Metzgeroth, and Nicholas C. P. Cross, “How I diagnose and treat myeloid/lymphoid neoplasms with tyrosine kinase gene fusions”
  • Alexandre Guy, Pierre-Emmanuel Morange, and Chloé James, “How I approach the treatment of thrombotic complications in patients with myeloproliferative neoplasms”

 

In the first How I Treat article, McMullin and Harrison discuss their approach to the use of cytoreduction in patients with low-risk polycythemia vera (PV).3 For high-risk patients (aged >60 years or history of thrombosis), standard care includes the addition of cytoreduction to the low-risk treatment backbone of low-dose aspirin and phlebotomy. In low-risk PV, progressive splenomegaly, leukocytosis, or thrombocytosis (eg, >1500 × 109/L); high symptom burden (related to PV and/or severe iron deficiency); and persistence of frequent phlebotomy are examples of indications that may justify the use of cytoreduction.1,2 In the last several years, molecular remission, eg, reduction of Janus kinase 2 (JAK2) V617F variant allele fraction, has increasingly animated the conversation between patients and physicians. This shift has likely been accelerated by the encouraging longer-term molecular results with ro-PEG-interferon-α-2b (BESREMi) in the CONTINUOUS-PV/PROUD-PV studies.4,5 Although molecular remission is an intuitively attractive therapeutic goal, it remains to be established whether such deeper responses will ultimately translate into disease modification (eg, reduction in thrombosis, decreased evolution to myelofibrosis [MF] or acute myeloid leukemia, and improved overall survival). Individuals without a conventional indication for cytoreduction (especially younger patients who have a longer survival runway ahead of them), may still wish to seek an active treatment plan. The “if and when” to use cytoreduction in the patient with low-risk PV is a complicated calculus of potential side effects, impact on quality of life, financial toxicity, and a hedge that committing to a long-term treatment program will favorably bend the arc of the disease.

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Advances in Blood Cancer Care for Veterans

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April 16, 2025| Federal Practitioner
Thomas Rodgers, MD

Hematologic malignancies encompass a broad range of distinct cancers, generally categorized as lymphoid (eg, lymphoma), myeloid (eg, leukemia, myelodysplastic syndromes, myeloproliferative neoplasms [MPNs]), and plasma cell neoplasms (eg, multiple myeloma).1 The veteran population is aging; this, in combination with other potential veteran-specific risk factors, is leading to an increased risk of hematologic malignancies.2 Of note, the risk for MPN diagnosis has recently been studied in veterans who served during the Korean, Vietnam, and Persian Gulf War eras.3 In addition, survival trends for different blood cancers, such as lymphoid malignancies, vary among veterans exposed to Agent Orange.4 Conflicting results have been found that point to the importance of future research.4 

Veterans in rural areas face barriers to treatment and clinical trial enrollment due to long travel distances and lack of trial availability, creating what are termed “clinical trial deserts.”5 Teleoncology has become crucial in bridging this gap by improving access to blood cancer treatments and clinical trials.5,6 Novel decentralized trial designs involving telehealth can further expand participation in remote areas.5

Over the past year, there have been advances in the treatment of blood cancers as well as the use of large data sets to better understand cancers trends and new technologies to reduce disparities in access to care.6,7 The availability of greater therapeutic options, new care modalities, and improved risk assessments herald an exciting time in the care of patients with hematologic malignancies, with the expectation that this care will continue to advance through 2025.

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Fedratinib Shows Promise in Long-Term MPN Success With Tolerable Toxicity

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By Hany Elmariah, MD

A phase 1 trial investigated the safety and tolerability of maintenance therapy with the JAK2 inhibitor fedratinib (Inrebic) following allogeneic hematopoietic cell transplant (HCT) for myeloproliferative neoplasms (MPNs) and myelodysplastic syndrome/MPN overlap syndromes.

While HCT offers potential cure for MPNs, posttransplant relapse remains a significant challenge. Fedratinib, effective in myelofibrosis, with a favorable safety profile and oral administration, presents a rational strategy to reduce relapse and potentially prevent graft-vs-host disease (GVHD) while preserving the graft-vs-tumor (GVT) effect.

“Usually with fedratinib, the main toxicities are cytopenia, so low blood counts. We also see a fair amount of [gastrointestinal (GI)] toxicity, nausea, vomiting, or diarrhea,” said Hany Elmariah, MD, associate member at the Moffitt Cancer Center in the Department of Bone Marrow Transplant and Cellular Immunotherapy, in an interview with Targeted OncologyTM.

The study enrolled patients post-HCT who received fedratinib between days +60 and +100 for up to 1 year. The trial utilized a 3+3 design to determine the maximum tolerated dose (MTD). Eleven patients were evaluable for dose-limiting toxicities (DLTs). The MTD was identified as 400 mg daily. While no DLTs occurred within the 30-day window, 4 patients withdrew due to non-DLT adverse events. Notably, only 1 patient developed severe chronic GVHD. The median progression-free survival was 12.4 months, and the 1-year overall survival was 100%.

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New Trial Will Assess Safety and Efficacy of MF Drug

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Leonardo Jaimes, MD

Publish Date

A clinical trial aiming to determine the efficacy, safety, and pharmacokinetics of the experimental drug WJ01024 combined with ruxolitinib in patients with myelofibrosis (MF) is set to begin soon.

“Although the clinical efficacy of ruxolitinib tablets has been confirmed, only about half of MF patients can achieve the ideal therapeutic effect (≥35% reduction in spleen volume and ≥50% improvement in disease symptoms at 24 weeks),” the authors wrote. “Therefore, there is an urgent need for innovative drugs that can be combined with ruxolitinib tablets to enhance therapeutic efficacy and meet clinical needs,” they added.

WJ01024 aims to enhance the therapeutic efficacy of ruxolitinib through  XPO-1 inhibition. Previous in vitro studies have confirmed that the drug enhances ruxolitinib anti-cell proliferation activity, the researchers noted. Furthermore, preliminary studies on humans suggest that WJ01024 is effective as monotherapy for relapsing patients and those intolerant to JAK inhibitors, they added.

The trial will consist of a dose escalation and a dose extension phase (phase 1a and phase 2). Phase 1b will divide patients into three groups receiving 40 mg, 60 mg, and 80 mg of WJ01024, respectively. Phase 2 will be an open-label evaluation of the efficacy and safety of the recommended dose in combination with ruxolitinib.

The study will only include patients diagnosed with MF and with the international prognostic scoring system risk category of intermediate-1, intermediate-2, or high-risk. Patients in the accelerated blast phase or previous treatment with either JAK or XPO-1 inhibitors are not eligible for participation.

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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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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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Safety and Efficacy of Busulphan Based on Dosing Patterns in the Real‐World Management of Myeloproliferative Neoplasms

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March 2025

Ali Mahdi, Alexandros Rampotas, Patrick Roberts, Joanna Stokes

Abstract

Introduction
Myeloproliferative neoplasms (MPNs), such as polycythaemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF), are primarily treated by managing blood counts to reduce the thrombotic risk using cytoreductive agents. Busulphan, an oral alkylating agent, has been historically used for MPN management due to its myelosuppressive effects, but concerns about its risk of leukaemic transformation have limited its use.
Methods
This real‐world retrospective study evaluated the safety and efficacy of busulphan in 115 MPN patients across 13 UK hospitals. Responses in patients with ET and PV only were assessed using European LeukemiaNet (ELN) criteria.
Results
With a median age of 78 years, the overall response rate was 78.1%, with 29% of PV and 18% of ET patients achieving complete responses. Dosing regimens were similarly distributed between repeated single doses of busulphan (31%), courses of treatment lasting 1–4 weeks (30%) and continuous therapy for more than 4 weeks (35%). No cases of disease progression to acute leukaemia or myelofibrosis were recorded during the median follow‐up of 23 months. Adverse events were infrequent, with fatigue and cytopaenia being the most common (4% each).
Conclusion
Busulphan demonstrated a favourable safety profile and is a viable cytoreductive option, particularly for elderly patients who are intolerant to hydroxycarbamide.

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

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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.

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

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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.