Defining the risk of clonal hematopoiesis and therapy-related myeloid neoplasms in multiple myeloma patients receiving ASCT and lenalidomide maintenance

Description

This project aims to determine whether DNA damage response–associated clonal hematopoiesis (DDR-CH) predicts therapy-related myeloid neoplasms in multiple myeloma patients receiving autologous stem cell transplantation and lenalidomide maintenance. Specific aims include characterizing CH prevalence at pre- and post-ASCT timepoints using ultra-deep error-corrected targeted sequencing, testing whether DDR-CH but not age-related CH confers tMN risk, and tracking serial clonal dynamics to determine whether lenalidomide selectively expands DDR-mutant clones. The project leverages a uniquely homogeneous placebo-controlled trial cohort to establish a causal link between therapy-selected CH and leukemogenesis, ultimately aiming to generate a risk classifier for prospective validation and clinical deployment.