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

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