Just me explaining mastocytosis and how i don't want to be pigeonholed into a sad montage of pictures of myself looking wistfully out the window lamenting how my life has changed. IT has changed, but accepting that can in and of itself be empowering.

Michael Deininger, MD, PhD, University of Utah, Salt Lake City, UT, presents findings from a mutational analysis of the Phase 1 EXPLORER trial (NCT02561988), which assessed avapritinib in patients with advanced systemic mastocytosis (AdvSM) and an associated hematologic neoplasm (AHN), primarily driven by KIT D816V mutations. Treatment with avapritinib in patients reported superior survival outcomes and significantly reduced KIT D816V disease burden in the majority of patients. Re-emergence of the mutations was additionally rarely seen in the patient cohort. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.

Daniel DeAngelo, MD, PhD, Chief, Division of Leukemia, Dana-Farber Cancer Institute, discusses treatment options available for systemic mastocytosis (SM).

SM is a rare, hematologic disorder most often caused by a mutation in the KIT D816V gene. The disorder is characterized by uncontrolled mast cell proliferation and activation across multiple organ systems, resulting in chronic, severe, and often unpredictable symptoms and extensive organ damage. A minority of SM patients have advanced SM, which encompasses a group of high-risk SM subtypes including aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL).

As Dr. DeAngelo explains, treatment options are dependent on the subtype of SM. Currently, there are no FDA approved treatments for indolent and smouldering SM, the less severe forms of the disease. For patients with these forms, supportive care in the form of antihistamines, leukotriene inhibitors, and/or corticosteroids is common. For patients with advanced SM, a few treatment options are available. Chemotherapy may be used to suppress mast cell count. Certain interferons can also do this. Additionally, there are two FDA-approved drug therapies for advanced SM. The first is midostaurin, which is a multi-targeted protein kinase inhibitor that was approved for the treatment of advanced SM in 2018. The second, and most recent, is avapritinib, which is a kinase inhibitor approved for the treatment of advanced SM in June 2021.

To learn more about SM and other rare hematologic disorders, visit checkrare.com/diseases/hematologic-disorders/

Mariana C. Castells MD, PhD, Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, and Professor of Medicine, Harvard Medical School, gives an overview of mastocytosis.

As Dr. Castells explains, mastocytosis is a rare, hematologic disorder most often caused by a mutation in the KIT D816V gene. The disorder is characterized by uncontrolled mast cell proliferation and activation across multiple organ systems, resulting in chronic, severe, and often unpredictable symptoms and extensive organ damage.

There are a number of mastocytosis subtypes, including cutaneous mastocytosis and systemic mastocytosis. The former primarily affects children and primarily involves the skin. In systemic mastocytosis, pathologic accumulation of mast cells is evident in tissue(s) other than skin – most commonly in bone marrow. Indolent systemic mastocytosis is generally associated with low mast cell burden and presence of mediator-related symptoms. Most patients with indolent systemic mastocytosis also have maculopapular skin lesions. Some patients may present with an enlarged liver or spleen and the gastrointestinal tract may also be affected. Life expectancy in patients with indolent systemic mastocytosis is comparable to the general population.

Recently, the results of TouchStone, a patient and healthcare provider (HCP) study on the burden and needs of patients living with systemic mastocytosis, were published in two papers titled "Patient-reported Outcomes Among Patients with Systemic Mastocytosis in Routine Clinical Practice: Results of the TouchStone SM Patient Survey" and "Perceptions of Patient Disease Burden and Management Approaches in Systemic Mastocytosis: Results of the TouchStone Healthcare Provider Survey.”