The Lynx Group

Assessment of Prognostic Scoring Tools for Systemic Mastocytosis in a Real-World Setting

Conference Correspondent

Systemic mastocytosis (SM) is a condition in which mast cells are overactivated and accumulate in various organs. Recent phase 1 and 2 clinical trials promoted development of new prognostic scoring systems to define and characterize SM and inform treatment strategies. However, these tools have not been sufficiently evaluated outside controlled studies in real-world clinical settings. In the current study, researchers evaluated the International Prognostic Scoring System for Mastocytosis (IPSM) and mutation-adjusted risk score (MARS) in a retrospective study to determine their ability to predict clinical outcomes and guide therapy decisions in patients with SM. Demographics, clinical data, and next-generation sequencing (NGS) gene panels were analyzed for 192 adult patients diagnosed with SM from 2009 to 2021 in a single center in the United Kingdom. For all patients with SM, prognosis was determined using the IPSM and prognosis for patients with advanced SM (AdvSM) was determined by MARS.

The cohort (n = 192) consisted of 46% males and 54% females, with a median age of 52 years (range, 5-84 years). Most of the patients were positive for KIT D816V mutations (68%). Patients were diagnosed with various SM subtypes: indolent SM (ISM; 67%), smoldering SM (SSM; 4%), and AdvSM (29%). AdvSM can be further categorized into SM with an associated hematologic neoplasm (78%), aggressive SM (17%), and mast-cell leukemia (5%).

After applying IPSM and MARS to SM and AdvSM, respectively, prognostic scores from both tools demonstrated an association between high-risk score and disease progression and worse clinical outcomes, including lower overall survival (OS). When applying IPSM, most cases of AdvSM were assigned AdvSM-3 (45%) or AdvSM-4 (18%), indicative of a greater number of observed risk factors (age >60 years, tryptase >125 ng/mL, hematologic parameters, skin involvement) and a greater number of reported deaths compared with AdvSM-1 and AdvSM-2. NGS myeloid gene panels indicated 18% of AdvSM patients were positive for ≥1 S/A/R mutations, which are associated with worse prognosis and are considered when applying MARS.

MARS scores categorized most of the AdvSM patients as low risk (51%) or intermediate risk (38%), which is associated with a greater probability of achieving 10-year OS. Only 13% of patients were assigned a high-risk prognosis with MARS. In addition, clinical progression of AdvSM was observed in 11% of patients, and progression to AHN was associated with the highest number of deaths (38%).

ISM and SSM (non-AdvSM) patients had better prognoses compared with those with AdvSM with median OS not reached in the non-AdvSM group and 12 months in the AdvSM group with 11-year follow-up. Evidence from the current assessment suggests IPSM and MARS may be useful tools for identifying high-risk patients to guide therapy toward more targeted first-line treatment options and improve outcomes. The researchers noted the relatively small sample size of the study and suggested further investigation of these and other developing prognostic tools in a larger cohort.

Sriskandarajah P, Oni C, Woodley C, et al. Application of prognostic scoring in systemic mastocytosis patients within a UK Centre of Excellence: Guys and St Thomas’ NHS Foundation Trust. 2021 American Society of Hematology Annual Meeting and Exposition; December 11-14, 2021. Abstract 3625.

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