LAUSR

Introduction Unprecedented depth of response is obtained with regimens incorporating monoclonal antibodies in the management of newly diagnosed multiple myeloma (NDMM). The incremental benefit of AHCT in this setting is being reconsidered but can be appraised by systematic assessment of disease burden pre- and post-AHCT utilizing NGS MRD. Methods We performed a multi-center clinical trial with Dara-KRd induction, AHCT (Melphalan conditioning), and post-AHCT, MRD response-adapted Dara-KRd consolidation.  Primary endpoint was MRD Results To date, 82 patients have been enrolled, and 77 (94%) have disease trackable by NGS. Of those, 54 have completed post-induction and 29 post-AHCT assessment.  The median age of the cohort is 61 years (range 36-79), with 46% females, 31% with high-risk FISH abnormality [t(4;14) or t(14;16) or del17p] and 20.3% ISS III disease. All patients obtained objective responses with the rate of best responses ≥VGPR of 93% after induction and 100% after AHCT and rate of sCR of 46% and 79%, respectively. MRD responses are displayed in Figure 1a. Patients with MRD Conclusion While a subset of patients with NDMM receiving Dara-KRD achieved MRD negativity after four cycles of induction, subsequent AHCT significantly increased the number of patients obtaining this status.   Despite a quadruple induction regimen utilizing what are considered the most effective anti-myeloma drugs, AHCT resulted in a substantial reduction of disease burden in a majority of patients and should remain part of current therapy for fit, NDMM patients.  Future trial designs with the intent to defer AHCT for patients may need to demonstrate high rates of MRD negativity to show benefit ultimately.