Systemic Mastocytosis (SM)

Mastocytosis is a heterogeneous disorder characterized by the abnormal growth and accumulation of morphologically and immunophenotypically abnormal mast cells (MCs) in 1 or more organs. The systemic form of the disease, systemic mastocytosis (SM), is characterized by diffuse and/or focal infiltration of neoplastic MCs in various organs including the bone marrow, spleen, liver, and gastrointestinal (GI) tract.¹ 

Disease manifestations are a result of direct infiltration with neoplastic MCs and release of mediators. Common mediators released by degranulating MCs are histamine, leukotriene C4, prostaglandin D2, chemokines, cytokines, and heparin. Symptomatic treatment of SM is directed at ameliorating the symptoms associated with the release of these mediators.² 

General Principles

Avoidance of triggers is recommended to avoid MC degranulation, and all patients should be offered symptomatic treatment. Common triggers include alcohol, aspirin, narcotics, contrast dye, and anesthetics.²

Those at risk of anaphylaxis should carry a self-injectable emergency EpiPen® (epinephrine). The first-line treatment for allergic symptoms such as pruritus and flushing are H1-receptor antagonists. Other therapies may be considered depending on disease severity and include epinephrine, corticosteroids, H2-receptor blockers, topical agents, aspirin, and leukotriene inhibitors.³ 

Physicians should familiarize themselves with the safety profiles of prescribed medications. For example, hydroxyzine (an H1-antagonist) should be used with caution in geriatric patients and those with glaucoma, benign prostatic hypertrophy, and asthma due to its cholinergic side effects. Leukotriene antagonists may impair liver function and are associated with neuropsychiatric adverse events. Prior to prescribing a medication, it is recommended to consult a comprehensive drug reference manual for detailed information regarding feasibility of use during pregnancy, black box warnings, specific contraindications, precautions, drug–drug interactions, and dose reduction for hepatic/renal dysfunction.³

Treatment Algorithm for Systemic Mastocytosis

Patients with indolent or smoldering SM primarily receive symptomatic management. They may undergo bone mineral density assessments and receive calcium and vitamin D supplements. Bisphosphonates are the first-line treatment for those with osteoporosis. In addition, immunomodulatory therapy with interferon-α (INF-α) has been shown to improve bone mineral density in SM patients with osteoporosis. A third-line treatment option includes cladribine. Patients in these disease categories may be enrolled in a clinical trial investigating potent, selective KIT inhibitors such as avapritinib.³

Patients with aggressive SM (ASM) may also enroll in a clinical trial investigating potent, selective KIT inhibitors. Midostaurin and cladribine are viable treatment options in this group, with midostaurin being preferred if rapid MC debulking is required. Additional therapies used in ASM include imatinib and INF-α. Patients with refractory disease may be candidates for allogeneic stem cell transplant.³

Patients with SM plus an associated hematologic neoplasm (SM-AHN) should undergo an assessment to determine which disease component warrants immediate treatment, taking into account clinical, histologic, and molecular data. For example, in patients with an aggressive AHN with low-burden or incidentally discovered SM, the AHN should be treated as per the standard of care with symptomatic management for SM. Patients with SM causing organomegaly with an indolent AHN should be treated as having ASM. Patients with SM-AHN should be restaged intermittently to assess the dominant component of progression.³ 

References

1. Lim KH, Tefferi A, Lasho TL, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood. 2009;113(23):5727-5736. doi:10.1182/blood-2009-02-205237

2. Mastocytosis. National Organization for Rare Disorders (NORD). Accessed April 13, 2022.

3. Pardanani A. Systemic mastocytosis in adults: 2021 update on diagnosis, risk stratification and management. Am J Hematol. 2021;96(4):508-525. doi:10.1002/ajh.26118

Reviewed by Harshi Dhingra, MD, on 4/15/2022.

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Kyle Habet, MD

Kyle Habet, MD, is a physician at Belize International Institute of Neuroscience where he is a member of a multidisciplinary group of healthcare professionals involved in the care of patients with an array of neurological and psychiatric diseases. He is a published author, researcher and instructor of neuroscience and clinical medicine at Washington University of Health and Science.