A Study to Evaluate the Efficacy and Safety of Daratumumab in Combination With Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to CyBorD Alone in Newly Diagnosed Systemic Amyloid Light-chain (AL) Amyloidosis
Summary
The purpose of this study is to evaluate the efficacy and safety of daratumumab plus cyclophosphamide, bortezomib and dexamethasone (CyBorD) compared with CyBorD alone in treatment of newly diagnosed amyloid light chain (AL) amyloidosis participants.
Timeline
- Start
- 2017-10-05
- Primary completion
- 2020-02-14
- Completion
- 2024-11-19
Outcome
Met primary endpoint
registry analysis (superiority test); CyBorD vs Daratumumab Plus CyBorD; p <0.0001; Odds Ratio (OR) 5.13 (95% CI 3.22 to 8.16); Cochran-Mantel-Haenszel NCT03201965 ↗
paper 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). PMID 42118698 ↗
release “Results from the ANDROMEDA study showed that the primary endpoint, hematologic CR rate, was 53 percent for D-CyBorD and 18 percent for CyBorD” jnj.com ↗
release “Janssen's ANDROMEDA study evaluated subcutaneous daratumumab in combination with bortezomib, cyclophosphamide, and dexamethasone (D-VCd) compared to VCd alone and met its primary endpoint” halozyme.com ↗
release “Daratumumab SC in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd) demonstrated significantly higher complete response rate in newly diagnosed patients with light chain (AL) amyloidosis” jnj.com ↗
Publications
- Kastritis E, Palladini G, Minnema MC, Wechalekar AD, Jaccard A, Lee HC, Sanchorawala V, Mollee P, Lu J, Schonland SO, Gatt ME, Suzuki K, Kim K, Cibeira MT, Bhutani M, Beksac M, Libby EN, Valent J, Hungria V, Rosenzweig MA, Bumma N, Huart A, Dimopoulos MA, Bhutani D, Waxman A, Goodman S, Zonder JA, Lam S, Song KW, Hansen T, Manier S, Roeloffzen WWH, Jamroziak K, Kwok F, Shimazaki C, Kim JS, Crusoe EQ, Tran N, Wang J, Chen Y, Vasey SY, Schecter JM, Vermeulen J, Comenzo R, Merlini G. Daratumumab-Bortezomib-Cyclophosphamide-Dexamethasone in Newly Diagnosed Amyloidosis: ANDROMEDA Final Survival Analysis. Blood. 2026 May 12:blood.2025032099. doi: 10.1182/blood.2025032099. Online ahead of print.
- Suzuki K, Wechalekar AD, Kim K, Shimazaki C, Kim JS, Ikezoe T, Min CK, Zhou F, Cai Z, Chen X, Iida S, Katoh N, Fujisaki T, Shin HJ, Tran N, Qin X, Vasey SY, Tromp B, Weiss BM, Comenzo RL, Kastritis E, Lu J. Daratumumab plus bortezomib, cyclophosphamide, and dexamethasone in Asian patients with newly diagnosed AL amyloidosis: subgroup analysis of ANDROMEDA. Ann Hematol. 2023 Apr;102(4):863-876. doi: 10.1007/s00277-023-05090-z. Epub 2023 Mar 2.
- Minnema MC, Dispenzieri A, Merlini G, Comenzo RL, Kastritis E, Wechalekar AD, Grogan M, Witteles R, Ruberg FL, Maurer MS, Tran N, Qin X, Vasey SY, Weiss BM, Vermeulen J, Jaccard A. Outcomes by Cardiac Stage in Patients With Newly Diagnosed AL Amyloidosis: Phase 3 ANDROMEDA Trial. JACC CardioOncol. 2022 Nov 15;4(4):474-487. doi: 10.1016/j.jaccao.2022.08.011. eCollection 2022 Nov.
- Kastritis E, Palladini G, Minnema MC, Wechalekar AD, Jaccard A, Lee HC, Sanchorawala V, Gibbs S, Mollee P, Venner CP, Lu J, Schonland S, Gatt ME, Suzuki K, Kim K, Cibeira MT, Beksac M, Libby E, Valent J, Hungria V, Wong SW, Rosenzweig M, Bumma N, Huart A, Dimopoulos MA, Bhutani D, Waxman AJ, Goodman SA, Zonder JA, Lam S, Song K, Hansen T, Manier S, Roeloffzen W, Jamroziak K, Kwok F, Shimazaki C, Kim JS, Crusoe E, Ahmadi T, Tran N, Qin X, Vasey SY, Tromp B, Schecter JM, Weiss BM, Zhuang SH, Vermeulen J, Merlini G, Comenzo RL; ANDROMEDA Trial Investigators. Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis. N Engl J Med. 2021 Jul 1;385(1):46-58. doi: 10.1056/NEJMoa2028631.
- Palladini G, Kastritis E, Maurer MS, Zonder J, Minnema MC, Wechalekar AD, Jaccard A, Lee HC, Bumma N, Kaufman JL, Medvedova E, Kovacsovics T, Rosenzweig M, Sanchorawala V, Qin X, Vasey SY, Weiss BM, Vermeulen J, Merlini G, Comenzo RL. Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA. Blood. 2020 Jul 2;136(1):71-80. doi: 10.1182/blood.2019004460.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Daratumumab | Monoclonal antibody | 1800 mg | Subcutaneous |
| Comparator | Bortezomib | Small molecule | 1.3 mg/m2 | Subcutaneous |
| Comparator | Cyclophosphamide | Other / unclassified | 300 mg/m2 | Oral |
| Comparator | Dexamethasone | Small molecule | 40 mg | Oral |