Target Therapies for Systemic Mastocytosis: An Update

Sciumè, Mariarita; Magistris, Claudio De De; Galli, Nicole; Ferretti, Eleonora; Milesi, Giulia; Roberto, Pasquale De De; Fabris, Sonia; Grifoni, Federica Irene

doi:10.3390/ph15060738

Cited by 7 publications

(4 citation statements)

References 70 publications

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“…In ISM and SSM, where the rate of progression is relatively low, only antimediator therapy is initially recommended. In ASM, cytoreductive therapy is recommended to prevent life-threatening mast cell proliferation since the rate of progression is quite high and survival is quite low [16] .…”

Section: Figure 1: Os and Pfs Of Patients With Asm Discussionmentioning

confidence: 99%

Clinical Characteristics of Patients with Aggressive Systemic Mastocytosis and Efficacy Analysis of Systemic Therapies: A Monocentric Real-World Experience

Açar,

Guvenc

2023

ijirms

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Introduction and Objective: Aggressive systemic mastocytosis is a lethal disease with poor prognosis in which organ damage due to mast cell activation is observed and response to medical treatment is low. The aim of this study was to evaluate the clinicopathological characteristics of ASM patients and the efficacy of cytoreductive treatments. Patients and methods: The clinicopathological features and survival analyses of 27 patients who were followed up with a diagnosis of aggressive systemic mastocytosis (ASM) and treated with cytoreductive therapy between 2017 and 2021 in our center were evaluated. Results: The mean age of the patients was 59 years and there was a slight male gender predominance (5: 4). KITD816V mutation was positive in 85% of cases. The most common symptoms at the time of diagnosis were fatigue, pruritus and dyspeptic complaints, respectively. The number of patients evaluable for response to imatinib, peginterferon alfa-2a (Peg-Ifn), cladribine and midostaurin treatments were 4, 7, 8 and 8, and the overall (partial) response rates were 25% (25%), 42% (28%), 50% (38%) and 37% (25%), respectively. Most of the responses were partial (PR) and major response (MR) was seen in very few patients. Increasing ECOG score, serum tryptase level, spleen size, and WBC count increased mortality, while decreasing hemoglobin level increased mortality. General median overall survival (OS) was 27.74 months (35.11-143.88). Two-year survival rate was 88.9% and 5-year survival rate was 63.1%. Median overall disease-free survival (DFS) was 10.86 months (9.27-12.50). Two-year DFS was 22.2%, while 5-year DFS was only 7.4%. Conclusion: The depth of response and response rates of the current therapies used in the treatment of ASM are quite low and insufficient to control the disease. Since there is an unmet therapeutic area in the treatment of ASM, there is a need for the development of new treatment modalities.

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Section: Figure 1: Os and Pfs Of Patients With Asm Discussionmentioning

confidence: 99%

Clinical Characteristics of Patients with Aggressive Systemic Mastocytosis and Efficacy Analysis of Systemic Therapies: A Monocentric Real-World Experience

Açar,

Guvenc

2023

ijirms

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“…Avapritinib (BLU-285, Ayvakit, Blueprint Medicines Corporation, Cambridge, MA, USA), a potent, highly selective inhibitor of KIT p.D816V, has been approved by the FDA for advanced SM (including ASM, SM-AHN, and MCL). Avapritinib treatment was associated with a marked reduction in symptoms and marrow MC burden, decreased tryptase level, spleen volume and KIT D816V VAF [130][131][132][133], and improved overall survival compared to midostaurin and cladribine [133]. The most common side effects are myelosuppression causing cytopenias, peripheral edema, periorbital edema, and fatigue [132].…”

Section: Advanced Sm (Asm Sm-ahn and Mcl)mentioning

confidence: 99%

Review and Updates on Systemic Mastocytosis and Related Entities

Li,

Ryder,

Zhang

et al. 2023

Cancers

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Mast cell disorders range from benign proliferations to systemic diseases that cause anaphylaxis and other diverse symptoms to mast cell neoplasms with varied clinical outcomes. Mastocytosis is the pathologic process of the accumulation of abnormal mast cells in different organs, mostly driven by KIT mutations, and can present as cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma. The WHO 5th edition classification divides systemic mastocytosis into bone marrow mastocytosis, indolent systemic mastocytosis, smoldering systemic mastocytosis, aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast cell leukemia. The new ICC classifies SM slightly differently. The diagnosis of SM requires the integration of bone marrow morphologic, immunophenotypic, and molecular findings, as well as clinical signs and symptoms. Moreover, understanding the wide range of clinical presentations for patients with mast cell disorders is necessary for accurate and timely diagnosis. This review provides an updated overview of mast cell disorders, with a special emphasis on SM, including the latest approaches to diagnosis, prognostic stratification, and management of this rare disease.

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“…Initial reports showed that the rare KITD816V negative cases were only responsive to first line TKI imatinib. New TKIs with activity against the KITD816V mutation, such as midostaurin or avapritinib have changed the management of this disease [6].…”

Section: Kit Inhibitionmentioning

confidence: 99%

The 2023 Updated Classification and Diagnostic Criteria of Mastocytosis

Hamed

2023

CTOIJ

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Mastocytosis is an uncommon hematologic malignancy characterized by accumulation of abnormal mast cells in various organs or tissues. A somatic point mutation in the KIT gene at codon 816 is detected in more than 90% of patients with systemic Masto cytosis (SM). The 2022 WHO classification continues to recognize three disease types: systemic mastocytosis, cutaneous mastocytosis and mast cell sarcoma. Bone marrow mastocytosis is a new separate subtype of SM. The classification also recognizes well-differentiated systemic mastocytosis, a morphologic pattern that can occur in any SM subtype. Diagnostic criteria for SM have been modified. The expression of CD30 and the presence of any KIT mutation causing ligand-independent activation have been accepted as minor diagnostic criteria. Classical B-findings and C-findings have undergone minor refinements. Most notably, variant allele frequency of D816V mutation ≥ 10% in bone marrow cells or peripheral blood leukocytes is qualified as a B-finding.

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Target Therapies for Systemic Mastocytosis: An Update

Cited by 7 publications

References 70 publications

Clinical Characteristics of Patients with Aggressive Systemic Mastocytosis and Efficacy Analysis of Systemic Therapies: A Monocentric Real-World Experience

Clinical Characteristics of Patients with Aggressive Systemic Mastocytosis and Efficacy Analysis of Systemic Therapies: A Monocentric Real-World Experience

Review and Updates on Systemic Mastocytosis and Related Entities

The 2023 Updated Classification and Diagnostic Criteria of Mastocytosis

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