A Snapshot Audit of Symptom Burden in Patients with Indolent Systemic Mastocytosis Utilising the ISM-SAF© within a UK Centre of Excellence: Guy’s and St Thomas’ NHS Foundation Trust

Background: Indolent systemic mastocytosis (ISM) is a rare, clonal haematological neoplasm driven by the KIT D816V mutation in up to 95% of cases. It is characterized by a debilitating, heterogenous and unpredictable symptom burden due to mast cell mediator release among patients. Treatment is limited to symptom management with no approved targeted therapies in the UK. The Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF^©) (Taylor et al. [2021]) is a validated symptom-assessment tool developed specifically for ISM patients focusing on 11 symptoms over a 24-hour recall period: bone pain, abdominal pain, nausea, skin spots, itch, flushing, fatigue, dizziness, brain fog, headache and diarrhoea. Each symptom is scored on a scale from 0-10. To date, there has not been any published UK data examining symptom burden in ISM patients. Subsequently we assessed symptom burden utilising the ISM-SAF^© in our patient cohort at Guy’s and St Thomas’ Hospital.

Method: All adult ISM patients who had a routine outpatient appointment between May 2022 and May 2023 were identified retrospectively. Over a four-week period, patients were invited to complete the ISM-SAF^© by telephone or in person. Additionally we collected demographic data, clinical data, anti-mediator therapy, anaphylaxis history and the impact of SM on their work and quality of life. All consultations were conducted by a clinical member of the mastocytosis team.

Results: 95 adult patients with ISM were identified within our database, of which 76 consented to take part in this study. There was a slight female predominance (41% male; 59% female) and the median age at diagnosis was 46 years (range 21 - 78). Median time to ISM diagnosis was 4.6 years (range 0.5-18.5). Median serum tryptase was 35 mcg/L (range 9-632). 66 patients (88%) were noted to have the KIT D816V mutation (6% D816V-negative, 6% not available). The median Total Symptom Score (TSS) was 24 (range 0-110). The highest scoring symptoms were fatigue (mean score 4.66), skin spots (3.97), brain fog (3.43) and itch (2.83). 33 patients (43%) had a TSS ≥28 which is the threshold determined by psychometric analysis to identify patients with moderate to severe symptoms, and is used for screening in clinical trials (Shields et al. [2023]). 46 patients (61%) were prescribed ≥2 anti-mediator therapies; at the time of the study, current therapies included H1 antihistamines (n=64), H2 antihistamines (n=28), proton pump inhibitors (n=20), sodium cromoglycate (n=18), montelukast (n=12), corticosteroid (n=5) and omalizumab (n=1). 12 patients (16%) were on a bisphosphonate. The number of patients with both a TSS ≥28 and on ≥2 anti-mediator therapies was 27 (36%). 30 patients (39%) reported a history of anaphylaxis at least once in their lifetime while 12% (n=9) reported using an adrenaline autoinjector within the last 12 months. There was no statistically significant correlation between TSS and serum tryptase (Pearson correlation coefficient r= -0.08, p=0.48). Some patients reported having to reduce their working hours, needing adjustments or retiring early due to symptoms attributed to their ISM diagnosis.

Conclusions: Our data demonstrate a significant real-world symptom burden among the ISM patient cohort within the UK Mastocytosis Centre of Excellence and reflect the findings of other centres, in particular fatigue being the most severe symptom (van Anrooij et al. [2016]; Mesa et al. [2022]). The ISM-SAF^© is an effective tool for capturing a snapshot of symptom severity and has utility in the outpatient setting. Importantly, we found over one third of patients in our centre had a TSS ≥28 and were on ≥2 anti-mediator therapies, meaning they could potentially be eligible to access tyrosine kinase inhibitors within the clinical trial setting.