The evaluation, management, and future of indolent systemic mastocytosis

Indolent systemic mastocytosis (ISM) is a chronic hematologic malignancy that has traditionally been managed primarily by allergists. However, with improved molecular diagnostics such as droplet digital PCR (ddPCR) for KIT D816V on bone marrow aspirate specimens and the availability of targeted therapies against KIT, hematologists are increasingly involved in the care of these patients. This review summarizes current understanding of the evaluation, diagnosis, treatment, and future therapeutic strategies in ISM, with a focus on clinically relevant insights for hematologists. We begin by emphasizing the broad and often debilitating range of ISM symptoms, which frequently include cutaneous, gastrointestinal, and mediator symptoms. The diagnostic workup underscores the importance of molecular testing for KIT mutations and bone marrow evaluation, clarifying the clinical scenarios in which each test should be utilized. Furthermore, management strategies start with symptomatic support and can include targeted KIT inhibition, such as avapritinib, for patients with refractory disease. ISM is a non-advanced subtype of systemic mastocytosis characterized by a wide spectrum of symptoms without evidence of organ damage. While many patients have stable disease, a subset may experience persistent morbidity or disease progression. Future directions include improving early recognition, validating biomarkers for monitoring and therapeutic response, and evaluating investigational therapies aimed at modifying disease course.