Anemia in myelofibrosis—prevalence, the U2AF1 connection, new treatments

Tefferi, Ayalew

doi:10.1038/s41408-017-0032-9

Cited by 8 publications

(10 citation statements)

References 10 publications

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“…[21,22] Often defined as a hemoglobin , 10 g/dL, anemia is present in approximately 36 to 50% of patients, and its incidence increases throughout the course of the disease. [23,24] When defined less stringently, anemia is found in nearly 90% of patients with MF. [24] In patients younger than 65, anemia is the clinical factor that most strongly affects survival and has been weighted accordingly in prognostic models.…”

Section: Anemiamentioning

confidence: 99%

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JAK Be Nimble: Reviewing the Development of JAK Inhibitors and JAK Inhibitor Combinations for Special Populations of Patients with Myelofibrosis

Kuykendall

Komrokji

2021

Journal of Immunotherapy and Precision Oncology

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Myelofibrosis (MF) is a myeloproliferative neoplasm hallmarked by uncontrolled blood counts, constitutional symptoms, extramedullary hematopoiesis, and an increased risk of developing acute myeloid leukemia. Janus kinase (JAK) inhibitors are the most common treatment for MF due to their ability to reduce spleen size and improve disease-related symptoms; however, JAK inhibitors are not suitable for every patient and their impact on MF is limited in several respects. Novel JAK inhibitors and JAK inhibitor combinations are emerging that aim to enhance the treatment landscape, providing deeper responses to a broader population of patients with the continued hope of providing disease modification and improving long-term outcomes. In this review, we highlight several specific areas of unmet need within MF. Subsequently, we review agents that target those areas of unmet need, focusing specifically on the JAK inhibitors, momelotinib, pacritinib, itacitinib, and NS-018 as well as JAK inhibitor combination approaches using CPI-0610, navitoclax, parsaclisib, and luspatercept.

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Section: Anemiamentioning

confidence: 99%

“…[23,24] When defined less stringently, anemia is found in nearly 90% of patients with MF. [24] In patients younger than 65, anemia is the clinical factor that most strongly affects survival and has been weighted accordingly in prognostic models. [22,25] Therapy-related anemia is also common.…”

Section: Anemiamentioning

confidence: 99%

JAK Be Nimble: Reviewing the Development of JAK Inhibitors and JAK Inhibitor Combinations for Special Populations of Patients with Myelofibrosis

Kuykendall

Komrokji

2021

Journal of Immunotherapy and Precision Oncology

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“…Anemia independently predicts shortened survival in MF, and TD-anemia categorizes an MF patient in the higher-risk category regardless of the presence or absence of other adverse risk factors [ 84 ]. Furthermore, anemia is the most common reason for ruxolitinib discontinuation [ 49 ].…”

Section: Agents In Clinical Development In Mf (Fig 1 mentioning

confidence: 99%

Novel therapeutics in myeloproliferative neoplasms

Venugopal

Mascarenhas

2020

J Hematol Oncol

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Hyperactive signaling of the Janus-Associated Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) pathway is central to the pathogenesis of Philadelphia-chromosome-negative myeloproliferative neoplasms (MPN), i.e., polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) which are characterized by inherent biological and clinical heterogeneity. Patients with MPNs suffer from substantial symptom burden and curtailed longevity due to thrombohemorrhagic complications or progression to myelofibrosis or acute myeloid leukemia. Therefore, the management strategies focus on thrombosis risk mitigation in PV/ET, alleviation of symptom burden and improvement in cytopenias and red blood cell transfusion requirements, and disease course alteration in PMF. The United States Food and Drug Administration’s (USFDA) approval of two JAK inhibitors (ruxolitinib, fedratinib) has transformed the therapeutic landscape of MPNs in assuaging the need for frequent therapeutic phlebotomy (PV) and reduction in spleen and symptom burden (PV and PMF). Despite improving biological understanding of these complex clonal hematopoietic stem/progenitor cell neoplasms, none of the currently available therapies appear to modify the proclivity of the disease per se, thereby remaining an urgent unmet clinical need and an ongoing area of intense clinical investigation. This review will highlight the evolving targeted therapeutic agents that are in early- and late-stage MPN clinical development.

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“…night sweats, weight loss and loss of appetite), variable degrees of splenomegaly and cytopenia, with significant anemia being a well-documented adverse prognostic feature, and an inherent risk of development of acute leukemia over the disease course. [2][3][4] Many advances in understanding disease pathogenesis followed the description of the somatic JAK2 V617F mutation in MPN by four groups in 2005 and the subsequent delineation of the role of CALR mutations in MF and other MPNs in 2012. [5][6][7][8][9] Multiple therapeutic agent targeting, either directly or indirectly, disease-associated deregulated JAK-STAT signaling have entered the clinical arena.…”

Section: Introductionmentioning

confidence: 99%

“… 22 Recent studies have additionally suggested an association between the presence of U2AF -spliceosome mutations and MF-related anemia. 4 Management strategies for anemia are varied and dependent on disease stage, degree of anemia, patient age, performance status, baseline endogenous erythropoietin levels, and available therapies. Frequently, those with significant anemia require RBC transfusions on a regular basis, with the inherent risk of alloimmunization, transfusion-related complications, and iron overload.…”

Section: Introductionmentioning

confidence: 99%

<p>Evaluating the Safety, Efficacy, and Therapeutic Potential of Momelotinib in the Treatment of Intermediate/High-Risk Myelofibrosis: Evidence to Date</p>

Bassiony

Harrison

McLornan

2020

TCRM

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Myelofibrosis is a heterogeneous disorder with regard to both molecular pathogenesis and clinical phenotype, ranging from an initial fairly indolent condition in some through to an aggressive and debilitating scenario with profound constitutional symptoms, cytopenia frequently requiring transfusional support, and massive splenomegaly. Many advances have been made within the therapeutic arena, and an increasing array of novel agents are now available for disease management. Within this review, we focus on the current and predicted role of the JAK inhibitor momelotinib (Sierra Oncology) in myelofibrosis, with an emphasis on clinical trial evaluation, drug efficacyand safety, and discuss the suggested place in the therapeutic paradigm of myelofibrosis in 2020 and beyond.

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Anemia in myelofibrosis—prevalence, the U2AF1 connection, new treatments

Cited by 8 publications

References 10 publications

JAK Be Nimble: Reviewing the Development of JAK Inhibitors and JAK Inhibitor Combinations for Special Populations of Patients with Myelofibrosis

JAK Be Nimble: Reviewing the Development of JAK Inhibitors and JAK Inhibitor Combinations for Special Populations of Patients with Myelofibrosis

Novel therapeutics in myeloproliferative neoplasms

<p>Evaluating the Safety, Efficacy, and Therapeutic Potential of Momelotinib in the Treatment of Intermediate/High-Risk Myelofibrosis: Evidence to Date</p>

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