Preliminary Evidence for Identifying Patterns of Organ Damage in Advanced Systemic Mastocytosis Subtypes

Systemic mastocytosis (SM) is a mast-cell neoplasm that typically involves overactivation and clumping of mast cells in various organs. Over time, SM can progress to advanced SM (AdvSM), which can be further categorized into 3 subtypes: SM with associated hematologic neoplasm (SM-AHN), aggressive SM (ASM), and mast-cell leukemia (MCL). AdvSM is often associated with a poor prognosis as a result of organ damage caused by mast-cell infiltration. However, few studies have extensively examined the typical clinical presentation profile (C-findings) of organ dysfunction across AdvSM subtypes. The retrospective analysis presented here compares definitions of C-findings to evaluate and characterize the distribution and incidence of organ damage at the time of initial presentation of AdvSM subtypes.

Organ damage in AdvSM includes hematologic and nonhematologic factors. These factors were initially defined by the World Health Organization (WHO) to characterize ASM. However, the definition of C-findings has evolved over time to include more clinically important and quantifiable criteria that are used to assess organ damage across all forms of AdvSM and determine eligibility for clinical trials. These tools include the International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis (IWG) and a modified version of these criteria (mIWG).

The current study identified 87 patients with a median age of 64 years (range, 24-88 years) at diagnosis with any form of AdvSM: ASM (15%), SM-AHN (72%), and MCL (13%). Of these patients, 53% were enrolled in clinical trials and had a median of 2 findings of organ damage as defined by WHO, IWG, or mIWG criteria. Irrespective of the criteria applied, there were no significant differences in organ damage identified among patients who had received 0, 1, 2, or more previous therapies. A significant difference was observed between the number of patients who met IWG/mIWG criteria for liver-related organ damage (P = .044) across all AdvSM subtypes. However, there was a greater proportion of patients with SM-AHN (P = .071) and MCL (P = .013) compared with ASM patients who met the IWG/mIWG-defined liver dysfunction criteria.

Hematologic findings observed in patients across subtypes included significantly different white blood cell, absolute neutrophil count, and monocyte counts. Overall, patients with SM-AHN had the highest median cell counts: white blood cell (11.4 × 10⁹/L), absolute neutrophil count (5.69 × 10⁹/L), and monocytosis (1.58 × 10⁹/L). The SM-AHN group also tended to have higher absolute eosinophil counts compared with ASM patients (P = .06). The results also indicated that patients with MCL had the highest need for red blood cell (55%) and platelet (27%) transfusions when using IWG/mIWG-defined red blood cell and platelet transfusion criteria. There was no evidence to support a difference in the number of IWG/mIWG nonhematologic organ damage findings across the 3 AdvSM subtypes. However, a pairwise comparison revealed a statistically higher number of IWG nonhematologic organ damage findings in patients with MCL compared with ASM.

These preliminary data suggest a pattern for hematologic organ damage findings in AdvSM subtypes when applying WHO, IWG, or mIWG criteria. Patients with SM-AHN had the highest blood cell counts, patients with MCL have the highest need for transfusion, and those with liver-associated organ damage appear to be more associated with SM-AHN and MCL compared with ASM. The researchers concluded that application of WHO, IWG, and mIWG criteria can be useful to assess organ damage patterns in patients with AdvSM receiving avapritinib.

Source
Liang EC, Perkins C, Lu R, et al. Organ damage at initial presentation across the spectrum of advanced systemic mastocytosis variants. American Society of Hematology Annual Meeting and Exposition; December 11-14, 2021. Abstract 2567.