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.

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Journal
Blood
Published
2026-05-12
DOI
https://doi.org/10.1182/blood.2025032099
Primary Topic
Amyloidosis: Diagnosis, Treatment, Outcomes
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article
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article

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

Moshe E. Gatt, Wilfried W. H. Roeloffzen, Jae‐Joong Kim, Michael Rosenzweig et al.
Blood
Amyloidosis: Diagnosis, Treatment, Outcomes
article

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

Moshe E. Gatt, Wilfried W. H. Roeloffzen, Jae‐Joong Kim, Michael Rosenzweig, Arnaud Jaccard, Naresh Bumma, NamPhuong Tran, J Lu, Jeffrey A. Zonder, Sandra Y. Vasey, Hans Chulhee Lee, Jessica Vermeulen, Monique C. Minnema, Timon Hansen, Edvan de Queiroz Crusoé, Chihiro Shimazaki, Edward N. Libby, Peter N. Mollee, Giampaolo Merlini, Kevin Song, Selay Lam, Stacey Goodman, Divaya Bhutani, Antoine Huart, Meletios-Athanasios A. Dimopoulos, Jason Valent, Raymond Comenzo, Adam Waxman, Manisha Bhutani, Yuping Chen, Vania Hungria, Giovanni Palladini, Krzysztof Jamroziak, Efstathios Kastritis, Vaishali Sanchorawala, Jianping Wang, Jordan M Schecter, Kenshi Suzuki, Stefan O. Schönland, Meral Beksac, Salomon Manier, Kihyun Kim, M Teresa Cibeira, Fiona Kwok, Ashutosh D. Wechalekar
article en

Abstract

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.

Blood
Boston University (US), Universidade Federal da Bahia (BR), Boston Medical Center (US), Tufts Medical Center (US), City Of Hope National Medical Center (US), Cleveland Clinic (US), Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA), University Medical Center Groningen (NL), Janssen (Belgium) (BE), Yonsei University (KR), Vanderbilt University (US), National and Kapodistrian University of Athens (GR), Peking University (CN), Heidelberg University (DE), University of Pavia (IT), Medical University of Warsaw (PL), Columbia University Irving Medical Center (US), Hadassah Medical Center (IL), London Health Sciences Centre (CA), The Royal Free Hospital (GB), Princess Alexandra Hospital (AU), Samsung Medical Center (KR), Vancouver General Hospital (CA), Westmead Hospital (AU), Kyoto Medical Center (JP), University Medical Center Utrecht (NL), Centre Hospitalier Universitaire de Lille (FR), Complexo Hospitalar Universitário Professor Edgard Santos (BR), Fred Hutch Cancer Center (US), The Barbara Ann Karmanos Cancer Institute (US), Levine Cancer Institute (US), Sarah Cannon (US), Japanese Red Cross Medical Center (JP), City of Hope (US), Michigan United (US), São Germano Oncologia (BR), Hospital Clínic de Barcelona (ES), Japanese American National Museum (US), Centre Hospitalier Universitaire de Limoges (FR), Istinye University (TR), Peking University People's Hospital (CN), Japan Community Healthcare Organization (JP), Dermatologikum Hamburg (DE), Janssen (United States) (US), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Janssen (Netherlands) (NL), University College London (GB), The Ohio State University (US), University of Pennsylvania (US)
Openalex Percentile: Top 8%
Amyloidosis: Diagnosis, Treatment, Outcomes
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