Comprehensive genomic and immune characterization of response and resistance to daratumumab-based quadruplet induction therapy

Description

This study aims to comprehensively characterize the genomic and immune landscape of newly diagnosed multiple myeloma (NDMM) patients treated with daratumumab-based quadruplet induction therapy (dara-quads). Preliminary data suggests that standard prognostic scores are inadequate for predicting outcomes, necessitating the inclusion of complex genomic and immune features. Specific Aim 1 focuses on identifying genomic features associated with response to dara-quads, including APOBEC mutational activity and intra-clonal heterogeneity. Specific Aim 2 aims to examine how immune composition may predict early relapse, in conjunction with genomic risk factors. The study utilizes both bulk and single-cell whole genome sequencing, along with immune assessment by CITE-seq, to provide a comprehensive understanding of NDMM treatment response and relapse prediction.