Daratumumab-bortezomib-cyclophosphamide-dexamethasone for newly diagnosed amyloidosis: ANDROMEDA final survival analysis

@article{kastritis2026daratumumabbortezomibcyclophosphamidedexamethasone,
  title = {{Daratumumab-bortezomib-cyclophosphamide-dexamethasone for newly diagnosed amyloidosis: ANDROMEDA final survival analysis}},
  author = {Efstathios Kastritis and Giovanni O. Palladini and Monique C. Minnema and Ashutosh D. Wechalekar and Arnaud Jaccard and Hans Chulhee Lee and Vaishali Sanchorawala and Peter N. Mollee and Jin Lu and Stefan O. Schönland and Moshe E. Gatt and Kenshi Suzuki and Kihyun Kim and M. Teresa Cibeira and Manisha Bhutani and Meral Beksaç and Edward N. Libby and Jason Neil Valent and Vânia Hungria and Michael Alan Rosenzweig and Naresh Bumma and Antoine Huart and Meletios Athanasios Dimopoulos and Divaya Bhutani and Adam Waxman and Stacey Ann Goodman and Jeffrey A. Zonder and Selay Lam and Kevin Song and Timon Hansen and Salomon Manier and Wilfried W. H. Roeloffzen and Krzysztof Jamroziak and Fiona Kwok and Chihiro Shimazaki and Jae‐Joong Kim and Edvan de Queiroz Crusoé and NamPhuong Tran and Jianping Wang and Yuping Chen and Sandra Y. Vasey and Jordan Mark Schecter and JESSICA T. VERMEULEN and Raymond L. Comenzo and Giampaolo Merlini and Bradley M. Augustson and Fiona Kwok and Peter Mollee and Simon DJ Gibbs and Chantal Doyen and Greet Bries and Isabelle Vande Broek and Ka Lung Wu and Koen Theunissen and Koen Van Eygen and Michel Delforge and Nathalie Meuleman and Philip Vlummens and Ângelo Maiolino and Breno Moreno De Gusmão},
  journal = {Blood},
  year = {2026},
  month = may,
  doi = {10.1182/blood.2025032099},
  url = {https://doi.org/10.1182/blood.2025032099},
  note = {CC BY-NC-ND},
}

TY  - JOUR
TI  - Daratumumab-bortezomib-cyclophosphamide-dexamethasone for newly diagnosed amyloidosis: ANDROMEDA final survival analysis
AU  - Efstathios Kastritis
AU  - Giovanni O. Palladini
AU  - Monique C. Minnema
AU  - Ashutosh D. Wechalekar
AU  - Arnaud Jaccard
AU  - Hans Chulhee Lee
AU  - Vaishali Sanchorawala
AU  - Peter N. Mollee
AU  - Jin Lu
AU  - Stefan O. Schönland
AU  - Moshe E. Gatt
AU  - Kenshi Suzuki
AU  - Kihyun Kim
AU  - M. Teresa Cibeira
AU  - Manisha Bhutani
AU  - Meral Beksaç
AU  - Edward N. Libby
AU  - Jason Neil Valent
AU  - Vânia Hungria
AU  - Michael Alan Rosenzweig
AU  - Naresh Bumma
AU  - Antoine Huart
AU  - Meletios Athanasios Dimopoulos
AU  - Divaya Bhutani
AU  - Adam Waxman
AU  - Stacey Ann Goodman
AU  - Jeffrey A. Zonder
AU  - Selay Lam
AU  - Kevin Song
AU  - Timon Hansen
AU  - Salomon Manier
AU  - Wilfried W. H. Roeloffzen
AU  - Krzysztof Jamroziak
AU  - Fiona Kwok
AU  - Chihiro Shimazaki
AU  - Jae‐Joong Kim
AU  - Edvan de Queiroz Crusoé
AU  - NamPhuong Tran
AU  - Jianping Wang
AU  - Yuping Chen
AU  - Sandra Y. Vasey
AU  - Jordan Mark Schecter
AU  - JESSICA T. VERMEULEN
AU  - Raymond L. Comenzo
AU  - Giampaolo Merlini
AU  - Bradley M. Augustson
AU  - Fiona Kwok
AU  - Peter Mollee
AU  - Simon DJ Gibbs
AU  - Chantal Doyen
AU  - Greet Bries
AU  - Isabelle Vande Broek
AU  - Ka Lung Wu
AU  - Koen Theunissen
AU  - Koen Van Eygen
AU  - Michel Delforge
AU  - Nathalie Meuleman
AU  - Philip Vlummens
AU  - Ângelo Maiolino
AU  - Breno Moreno De Gusmão
PY  - 2026
DA  - 2026/05/12
JO  - Blood
DO  - 10.1182/blood.2025032099
UR  - https://doi.org/10.1182/blood.2025032099
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.
SN  - 0006-4971
SN  - 1528-0020
ER  -