TY - JOUR
T1 - Daratumumab-bortezomib-cyclophosphamide-dexamethasone for newly diagnosed amyloidosis
T2 - ANDROMEDA final survival analysis
AU - ANDROMEDA Trial Investigators
AU - Kastritis, Efstathios
AU - Palladini, Giovanni
AU - Minnema, Monique C.
AU - Wechalekar, Ashutosh D.
AU - Jaccard, Arnaud
AU - Lee, Hans C.
AU - Sanchorawala, Vaishali
AU - Mollee, Peter
AU - Lu, Jin
AU - Schönland, Stefan
AU - Gatt, Moshe E.
AU - Suzuki, Kenshi
AU - Kim, Kihyun
AU - Cibeira, M. Teresa
AU - Bhutani, Manisha
AU - Beksac, Meral
AU - Libby, Edward
AU - Valent, Jason
AU - Hungria, Vania
AU - Rosenzweig, Michael
AU - Bumma, Naresh
AU - Huart, Antoine
AU - Dimopoulos, Meletios A.
AU - Bhutani, Divaya
AU - Waxman, Adam J.
AU - Goodman, Stacey A.
AU - Zonder, Jeffrey A.
AU - Lam, Selay
AU - Song, Kevin
AU - Hansen, Timon
AU - Manier, Salomon
AU - Roeloffzen, Wilfried
AU - Jamroziak, Krzysztof
AU - Kwok, Fiona
AU - Shimazaki, Chihiro
AU - Kim, Jin Seok
AU - Crusoe, Edvan
AU - Tran, Nam Phuong
AU - Wang, Jianping
AU - Chen, Yuping
AU - Vasey, Sandra Y.
AU - Schecter, Jordan M.
AU - Vermeulen, Jessica
AU - Comenzo, Raymond L.
AU - Merlini, Giampaolo
AU - Augustson, Bradley
AU - Kwok, Fiona
AU - Mollee, Peter
AU - Gibbs, Simon
AU - Doyen, Chantal
N1 - Publisher Copyright:
© 2026 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. This is an open access article under the CC BY-NC-ND license. http://creativecommons.org/licenses/by-nc-nd/4.0/
PY - 2026/8/27
Y1 - 2026/8/27
N2 - In the primary analysis of ANDROMEDA, addition of subcutaneous daratumumab to VCd (bortezomib, cyclophosphamide, and dexamethasone; D-VCd) significantly improved hematologic complete response (CR) rate vs 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 6 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 end point was hematologic CR. The updated hematologic CR rate was 59.5% for D-VCd vs 19.2% for VCd (odds ratio, 6.03; 95% confidence interval [CI], 3.80-9.58; P < .0001). Median time to hematologic CR was shorter with D-VCd (67.5 days [range, 8.0-879.0]) vs 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 vs VCd in major organ deterioration–progression-free survival (hazard ratio, 0.44; 95% CI, 0.31-0.63; P < .0001) and overall survival (hazard ratio, 0.62; 95% CI, 0.42-0.90; P = .0121). Cardiac and renal response rates were 2 to 3 times higher with D-VCd vs 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 organ function recovery, translating to statistically significant improvement in both overall survival and major organ deterioration–progression-free survival in newly diagnosed AL amyloidosis. This trial was registered at www.clinicaltrials.gov as #NCT03201965.
AB - In the primary analysis of ANDROMEDA, addition of subcutaneous daratumumab to VCd (bortezomib, cyclophosphamide, and dexamethasone; D-VCd) significantly improved hematologic complete response (CR) rate vs 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 6 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 end point was hematologic CR. The updated hematologic CR rate was 59.5% for D-VCd vs 19.2% for VCd (odds ratio, 6.03; 95% confidence interval [CI], 3.80-9.58; P < .0001). Median time to hematologic CR was shorter with D-VCd (67.5 days [range, 8.0-879.0]) vs 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 vs VCd in major organ deterioration–progression-free survival (hazard ratio, 0.44; 95% CI, 0.31-0.63; P < .0001) and overall survival (hazard ratio, 0.62; 95% CI, 0.42-0.90; P = .0121). Cardiac and renal response rates were 2 to 3 times higher with D-VCd vs 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 organ function recovery, translating to statistically significant improvement in both overall survival and major organ deterioration–progression-free survival in newly diagnosed AL amyloidosis. This trial was registered at www.clinicaltrials.gov as #NCT03201965.
UR - https://www.scopus.com/pages/publications/105042600610
U2 - 10.1182/blood.2025032099
DO - 10.1182/blood.2025032099
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C2 - 42118698
AN - SCOPUS:105042600610
SN - 0006-4971
VL - 148
SP - 1097
EP - 1107
JO - Blood
JF - Blood
IS - 9
ER -