Interim Analysis of Mmrf Curecloud Research Initiative Identifies High Prevalence and Patterns of Clonal Hematopoiesis of Indeterminate Potential (CHIP) Mutations in a Real World Myeloma Cohort

Background: In order to gain a deeper understanding of the clinical, molecular and immune parameters involved in multiple myeloma (MM) disease initiation, progression and response to treatment, the Multiple Myleoma Research Foundation (MMRF) and its partners launched the CureCloud Research Initiative (NCT03657251), a Direct-to-Patient (DTP) effort aimed at enrolling 5,000 individuals from whom comprehensive molecular and immune analyses are generated from blood specimens and the resulting data aggregated with the correlating clinical information. Methods: To support the molecular characterization of liquid biopsies for CureCloud, a set of myeloma-specific blood-based approaches were developed. The first of such assays is a hybrid selection panel that captures 70 commonly altered MM and Clonal Hematopoiesis of Indeterminate Potential (CHIP) genes detecting somatic variants present in a patient's circulating-free DNA (cfDNA). This MM-70 assay was thoroughly validated to >90% sensitivity for events at 1% variant allele frequency with a specificity of 0.1) CHIP Variant Allelic Fractio