Predicting therapy-related myeloid neoplasms after CAR-T with the Clonal Haematopoiesis Risk Score (CHRS)

Abstract

The clonal haematopoiesis risk score (CHRS) was proposed to predict the rate of progression from clonal haemopoiesis of indeterminate potential (CHIP)/clonal cytopenia with unknown significance (CCUS) to myeloid neoplasms in the general population. CHRS encompasses the type and VAF of the mutation, the presence of a single DNMT3A mutation, cytopenia, age, red cell distribution width (RDW) and mean corpuscular volume (MCV). We studied clonal haematopoiesis in a cohort of 55 consecutive patients treated with CD19-directed CAR-T cells: CHIP and CCUS were present in 7% and 33% of patients before CAR-T. Three therapy-related myeloid neoplasms (t-MN) were observed after treatment with CAR-T (2 MDS and 1 AML). Only patients with an intermediate-high baseline CHRS developed a t-MN. Patients with an intermediate-high CHRS had more than a twofold increased risk of developing a t-MN within the first 9 months after CAR-T (odds ratio 2.89, 95% C.I. 1.98-4.19, p < 0.001). Overall, CHRS was able to predict the occurrence of t-MN after CAR-T with good specificity.