Systemic Mastocytosis Patient Experience from Mast Cell Connect, the First Patient-Reported Registry for Mastocytosis
Authors: Lee Philina , George Tracy I. , Shi Hongliang , Evans Erica K. , Singh Teghpal , Boral Anthony L , Rangel Miller Vanessa , Verstovsek Srdan 
Published: October 2019

Abstract
Background:
Systemic mastocytosis (SM) is a rare mast cell disorder associated with a range of debilitating symptoms and a shortage of effective treatment options. Little is known about the impact of the disease from the patients' perspective. Systematically characterizing the natural history of SM and its impact on patients will facilitate the development of new therapies. Registries that engage patients have proven valuable in other rare diseases by expanding knowledge of current treatment approaches, evaluating disease burden and accelerating clinical trials.
Methods:
Mast Cell Connect (NCT02620254, www.mastcellconnect.org) is an observational database that captures demographic, socioeconomic and disease information from patients with mastocytosis. It is the first patient-reported registry for mastocytosis to our knowledge. Key objectives are to improve collective understanding of the disease burden on patients and to facilitate development of new therapies by increasing participation in clinical trials. Enrollment is "site-agnostic" as participants register and take surveys on a secure online portal. Since many US patients are seen outside large clinical centers, this enables broader participation and collection of real-world data. Inclusion criteria are a diagnosis of SM or cutaneous mastocytosis (CM). Diagnoses are self-reported and participants are asked to provide medical reports that will be used to confirm diagnoses in the future. Informed consent is required to join this IRB-approved study.
Results:
Mast Cell Connect opened on December 1, 2015. As of May 31, 2016, 166 participants had registered, of whom 157 had responded to the online survey. Of the 153 participants who reported their diagnosis, 107 had SM and 38 had CM. Those who reported a diagnosis of SM were categorized as SM participants if they also reported other diagnoses. The current analyses are based on data provided by the 107 SM participants.
Of the 107 SM participants, 60 (56%) had Indolent SM (ISM), 8 (7%) had Smoldering SM (SSM), 10 (9%) had Advanced SM (AdvSM, defined as aggressive SM, SM with an associated hematological neoplasm, and Mast Cell Leukemia) and 29 (27%) did not know their subtype. Median age was 50 years (range 4-77). More females participated (74%) than males (26%). Median time from symptom-onset to diagnosis was 7 years. Participants saw a median of 3 specialists prior to diagnosis, most frequently dermatology (67%), allergy/immunology (67%), hematology/oncology (63%) and general practitioner/internal medicine (63%). Specialists diagnosing SM most often included dermatology (36%), allergy/immunology (25%) and hematology/oncology (23%). AdvSM participants were typically diagnosed by hematology/oncology (70%).
The medications taken most often at the time of survey were anti-histamines (85% H1 blockers, 72% H2 blockers), leukotriene inhibitors (38%) and cromolyn sodium (33%). Agents to reduce mast cell burden were taken less often (imatinib: 7%, interferon-α: 2%, hydroxyurea: 1% and investigational agents: 1%). Symptoms reported as moderately to severely bothersome included: fatigue (69%), difficulty concentrating (63%), abdominal pain (55%), pain in other locations (53%), difficulty sleeping (53%), itching (46%), diarrhea (45%), bloating (43%), nausea (42%), headache (40%), skin changes (40%), anxiety (39%) and flushing (37%). Participants reported being limited in work or other daily activities "quite a bit" to "very much" in 47% of ISM, 43% of SSM, and 70% of AdvSM cases. Participants' physical condition or medical treatment interfered with their family life "quite a bit" or "very much" in 59% of ISM, 43% of SSM, and 80% of AdvSM cases.
Conclusions:
Over 160 participants joined Mast Cell Connect in the first 6 months, indicating the mastocytosis community, including The Mastocytosis Society, is highly motivated to participate in research. SM participants reported a diagnostic odyssey, seeing multiple specialists over a median of 7 years prior to diagnosis. Despite frequent use of symptom-directed medications, symptom burden remains substantial and considerably impacts quality of life. Novel therapies targeting the underlying disease are needed. Establishing US centers of excellence may hasten the time to diagnosis. Continued collaboration between researchers, patient advocates and industry is needed to advance the care of patients with SM.

Disclosures
Lee: Blueprint Medicines: Employment, Equity Ownership. George:Allakos: Research Funding; Novartis: Consultancy; Blueprint Medicines: Consultancy; Allakos: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Research Funding; Incyte: Consultancy; GLG: Consultancy; Wiley Blackwell: Consultancy; American Registry of Pathology: Patents & Royalties; Wolters Kluwer: Patents & Royalties; UpToDate: Patents & Royalties. Shi:Blueprint Medicines: Employment, Equity Ownership. Evans:Blueprint Medicines: Employment, Equity Ownership. Singh:Blueprint Medicines: Employment, Equity Ownership. Boral:Blueprint Medicines: Employment, Equity Ownership. Rangel Miller:PatientCrossroads: Employment, Equity Ownership.