The mutation-adjusted Risk Score (MARS) and advanced systemic mastocytosis (SM) World Health Organization (WHO) classification system appear to have the highest prognostic value for advanced SMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm. patients treated with midostaurin, according to a recently published study in the American Journal of Hematology.
WHO classifies SM into four main subtypes: bone marrow mastocytosisBone marrow mastocytosis A subtype of indolent SM that occurs when the excess mast cells accumulate in the bone marrow, but not the skin or other organs. (BMM), indolent SMIndolent SM A subtype of nonadvanced SM caused by the abnormal accumulation of mast cells in the bone marrow and other organs. Indolent SM accounts for around 90% of SM cases., smoldering SMSmoldering SM A subtype of nonadvanced SM, with a higher mast cell burden than the indolent subtype. Smoldering SM has a higher likelihood of progressing to an advanced form., SM associated with hematological neoplasm (SM-AHN), mast cell leukemiaMast cell leukemia The most severe subtype of SM, caused by the rapid buildup of immature mast cells in the bone marrow and blood. Mast cell leukemia accounts for less than 5% of SM cases and has a poor prognosis. (MCL), and aggressive SMAggressive SM A subtype of advanced SM marked by a high mast cell burden that leads to organ damage. Aggressive SM accounts for less than 10% of SM cases..
The advanced mastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults. group comprises aggressive SM, SM associated with hematological neoplasm and mast cell leukemia. Patients with advanced mastocytosis tend to have a poorer prognosis due to an increased risk of progressing acute myeloid leukemia (AML).
Additionally, patients in this group tend to have clinical indicators of organ damage such as skeletal lesions, increased liver size (hepatomegaly), anemia, and low white blood cell counts. These indicators are known as c-findings and are associated with a poor prognosis.
Learn more about SM prognosis
Since the introduction of KIT-D816V-targeted tyrosine kinase inhibitors (TKIs) such as midostaurin, the prognosis of patients with advanced SM has significantly improved, with treatment response rates reaching 60%, according to some studies.
Varied outcomes according to each SM subtype
New therapeutic alternatives have created a need for prognostic tools that enable physicians to identify patients with higher risk within each SM subtype to develop treatment plans tailored to individual risk. Therefore, the authors aimed to assess the accuracy of the several available prognostic scores for SM. The study included data from 170 patients with advanced SM who were treated with midostaurin.
Of the 170 selected patients, 46 had aggressive SM, 11 mast cell leukemia and 114 SM associated with hematological neoplasm. There was no significant difference in the incidence of c- findings among groups. Genetic workup revealed that patients with SM-AHN were more likely to have high-risk mutations.
Researchers observed that patients’ responses to midostaurin varied significantly. Patients with aggressive AM had the best response (73%), followed by SM associated with hematological neoplasm (50%) and mast cell leukemia (27%).
Approximately 50% of patients died 19 months after beginning treatment; the highest mortality rates were among the mast cell leukemia and SM associated with hematological neoplasm groups (57% and 55%), and the aggressive SM group had a mortality rate of 35%.
Through statistical analysis, the comparison between MARS, the International Prognostic Scoring System for mastocytosis (IPSM) and the Global Prognostic Score for Systemic Mastocytosis (GPSM) revealed that the combination of WHO subtype classification and MARS had the best prognostic accuracy.
“Based on these variables, five subgroups of AdvSMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm. patients with distinct outcomes have been identified, highlighting the need for specific management,” the authors wrote. “Further studies are critically needed to determine if this prognostic characterization remains relevant in AdvSM patients treated with other TKIs.”
