Abstract
Introduction. Idiopathic mast cell activation syndrome (MCAS) is an immunologic disorder characterized by inappropriate activation and degranulation of mast cells. Similar to other mast cell disorders, such as systemic mastocytosis (SM), MCAS can have very diverse clinical presentations, making diagnosis and treatment challenging. Standard treatment options include antihistamines, mast cell stabilizers, and inhibitors of mast cell mediator production or release. However, patient response to these therapies can be just as varied as their presentations. As a result, further treatment options are necessary to appropriately address MCAS and reduce burden on patient health-related quality of life. Imatinib is approved for the treatment of c-KIT wild-type SM, but has more recently found use in MCAS as reported in multiple cases in the literature. To our knowledge, this is the first retrospective study examining the use and efficacy of imatinib for MCAS in a larger cohort of patients.
Methods. This single-center, retrospective study was conducted through review of electronic health records from a community hematology clinic (Asplundh Cancer Center) between February 2020 and July 2025. Inclusion criteria were 1) patients of age 18 or older who, 2) were diagnosed with MCAS, and 3) treated with imatinib. Patients were excluded if they had a diagnosis of, or suspicion for, other mast cell disorders. Prior to imatinib treatment, all patients were confirmed to not have a c-KIT D816V mutation. For each patient, record review was conducted for 6 months prior to and 6 months following the initiation of imatinib. All symptoms during this period were recorded and graded on a scale of severity and frequency modeled after a Likert scale. A composite score was obtained by multiplying individual scores for every symptom and was recalculated at intervals of 3 months during the observation period.
Results. Between February 2020 and July 2025, 29 patients were treated with imatinib for MCAS. One patient had incomplete records and was excluded from analysis. Notably, 26/28 (93.1%) patients identified as White/Caucasian females. The remaining two patients were both male, with one identifying as White/Caucasian and the other as Hispanic/Latino. 23/28 patients were ≤ 45 years old. Imatinib was dosed at 200 mg/day, although some patients were initiated at a dose of 100 mg/day with later dose escalation. Prior to initiation of imatinib, all patients received multiple lines of treatment for MCAS without resolution of their symptoms and remained on these other medications throughout the observation period.
Six patients displayed a complete response (CR), defined as a reduction in MCAS symptoms to less than monthly occurrence on chronic therapy. Sixteen patients had a reduction in symptom score of ≥ 40%, indicating partial response (PR). The overall response rate was 78.6% (95%CI: 59.0-95.3%). 19/22 (86.4%) patients achieved CR/PR within 3 months. Patients who had reached PR at 3 months had no significant further change in response at 6 months. Change in raw score was not included in the analysis due to diversity in baseline symptomatology.
Conclusion. Our results show that patients with MCAS treated with imatinib benefitted from decreased symptom severity and frequency. Many patients demonstrated repeated flares with certain exposures, such as heat, or certain procedures, such as joint injections and tunneled port accession. In these cases, the addition of imatinib not only helped with their MCAS symptoms but also helped with the management of other comorbidities. This study was designed to be a pilot and opens the door for future prospective studies that can evaluate imatinib both in conjunction with, and independent of, other treatments for MCAS.
