A new prognostic score confirmed that KIT Inhibitors improve outcomes in patients with advanced systemic mastocytosis (SM), according to a study recently published in the American Society of Hematology Annual Meeting and Exposition.
“We … sought (i) to assess the prognostic superiority of KIT inhibitor-treated patients compared to KIT inhibitor-naïve patients and (ii) to devise a risk stratification algorithm specifically designed for patients undergoing treatment with KIT inhibitors,” the authors said.
What is a KIT gene mutation?
SM is usually caused by a sporadic mutation in the KIT gene, which codes for a protein called CD117 transmembrane tyrosine kinase. The protein is involved in the growth, survival and migration of mast cells. The most common KIT mutation associated with SM is the D816V mutation, which results in the amino acid aspartic acid being replaced by the amino acid valine in the protein chain.
The new risk score successfully reflected the positive effect of KIT-inhibitor therapy on the prognosis of advanced SM (AdvSM), the study found.
Read more about SM therapies
Current prognostic scores for advanced SM, such as the mutation-adjusted risk score (MARS) or the international prognostic scoring system (IPSM), were developed before the introduction of KIT-inhibitor therapy and do not take into account its effect on overall survival.
The authors collected data from more than 200 patients with KIT D816V positive advanced SM and compared outcomes between patients undergoing KIT-inhibitor therapy and those receiving other forms of treatment. Additionally, they analyzed clinical and genetic variables that correlated with an improved or worsened overall survival.
As expected, the novel risk score revealed that receiving KIT-inhibitor therapy improved advanced SM prognosis.
The risk score also detected six factors associated with shorter overall survival in patients with advanced SM.
- Higher age.
- Lower hemoglobin levels.
- Higher monocyte levels.
- Increased number of mutations in the high-risk panel SRSF2/ASXL1/RUNX1.
- Cytogenetic abnormalities.
- Absence of skin involvement.
Based on whether patients received KIT inhibitors and the presence of the six risk factors, the risk score classified patients into four subgroups: low risk, intermediate risk 1, intermediate risk 2 and high risk. The new risk score had higher prognostic accuracy for overall survival and leukemia-free survival than MARS and IPSM.
“The proposed risk-score offers a contemporary four-tier risk categorization for [overall survival] and [leukemia-free survival] in KIT D816V positive AdvSM patients on treatment with KIT inhibitors and may serve as a valuable tool for clinicians when considering intensifying treatment, e.g. with allogeneic hematopoietic cell transplantation,” the authors said.
