Daratumumab-Bortezomib-Cyclophosphamide-Dexamethasone in Newly Diagnosed Amyloidosis: ANDROMEDA Final Survival Analysis

In the primary analysis of ANDROMEDA, addition of subcutaneous daratumumab to bortezomib/cyclophosphamide/dexamethasone (D-VCd) significantly improved hematologic complete response (CR) rate versus VCd, establishing D-VCd as the only approved therapy for light-chain (AL) amyloidosis. We present results from the preplanned final analysis. In this phase 3 trial, we randomly assigned 388 patients with newly diagnosed AL amyloidosis to six cycles of VCd alone (control group) or with subcutaneous daratumumab (D-VCd) followed by single-agent daratumumab every 4 weeks for up to 24 total cycles. The primary endpoint was hematologic CR. The updated hematologic CR rate was 59.5% for D-VCd versus 19.2% for VCd (odds ratio, 6.03; 95% confidence interval [CI], 3.80-9.58; P<0.0001). Median time to hematologic CR was shorter with D-VCd (67.5 days [range, 8.0-879.0]) versus VCd (85.0 days [range, 14.0-617.0]). With a median follow-up of 61.4 months, significant improvement was observed with D-VCd versus VCd in major organ deterioration-progression-free survival (hazard ratio, 0.44; 95% CI, 0.31-0.63; P<0.0001) and overall survival (hazard ratio, 0.62; 95% CI, 0.42-0.90; P=0.0121). Cardiac and renal response rates were 2-3 times higher with D-VCd versus VCd. Achieving hematologic or cardiac CR was associated with improved major organ deterioration-progression-free survival and overall survival. Adverse events were consistent with the known safety profiles for VCd and daratumumab. Adding daratumumab to VCd resulted in deeper and more rapid hematologic responses and recovery of organ function, translating to statistically significant improvement in both overall survival and major organ deterioration-progression-free survival in newly diagnosed AL amyloidosis. ClinicalTrials.gov NCT03201965.