Abstract Quadruplet induction, autologous hematopoietic cell transplant (AHCT), and measurable residual disease (MRD) response‐adapted consolidation yield an unprecedented depth of response in newly diagnosed multiple myeloma. Patients treated on MASTER (NCT03224507) ceased therapy and entered active surveillance (MRD‐SURE) after achieving MRD negativity. This study characterizes quantitative changes in the immunoglobulin (Ig) gene repertoire by next‐generation sequencing and serum gamma globulin levels. Quadruplet therapy leads to profound hypogammaglobulinemia and reduction in the Ig gene repertoire. Immune reconstitution (IR) is delayed in patients who received post‐AHCT consolidation compared to those who do not. Eighteen months after treatment cessation, there was no statistically significant difference between the groups.
