FDA Approves Daratumumab and Hyaluronidase Plus VCd for Newly Diagnosed Light Chain Amyloidosis
Key Clinical Takeaways
- Clinical Relevance: The FDA has approved daratumumab and hyaluronidase in combination with VCd for the treatment of newly diagnosed patients with AL amyloidosis, providing clinicians with a new standard of care.
- Design/Population: In the phase 3 ANDROMEDA trial, 388 patients with at least one affected organ were randomized 1:1 to receive VCd alone or in combination with daratumumab and hyaluronidase.
- Key Outcomes: At analysis, daratumumab and hyaluronidase improved both major organ deterioration PFS (HR, 0.47; 95% CI, 0.33–0.67; P<.0001) and OS (HR, 0.62; 95% CI, 0.42–0.90; P = .0121). Caution is warranted for patients with advanced cardiac involvement (NYHA class IIIB/IV or Mayo stage IIIB), and ongoing monitoring for cardiac and hematologic toxicities is recommended.
On November 19, 2025, the US Food and Drug Administration (FDA) approved daratumumab and hyaluronidase in combination with bortezomib, cyclophosphamide, and dexamethasone (VCd) for the treatment of newly diagnosed patients with light chain (AL) amyloidosis. This conversion to traditional approval was based on results from the phase 3 ANDROMEDA trial.
In this open-label, active-controlled study, 388 patients with measurable disease and at least one affected organ per consensus criteria were randomized to receive either VCd alone or in combination with daratumumab and hyaluronidase. The primary end point was major organ deterioration progression-free survival (PFS). A key secondary end point was overall survival (OS).
At a median follow-up of 61.4 months, median major organ deterioration PFS was not reached in the daratumumab and hyaluronidase arm and 30.2 months in the VCd arm (hazard ratio [HR] 0.47; 95% confidence interval [CI], 0.33 to 0.67; P = .0001). The median OS was not reached in either arm (HR 0.62; 95% CI, 0.42 to 0.90; P = .0121).
The recommended dose is 1,800 mg of daratumumab and 30,000 units of hyaluronidase administered subcutaneously into the abdomen over approximately 3-to-5 minutes in combination with VCd according to the recommended dosing schedule.
Prescribing information includes warnings and precautions for cardiac toxicities, including serious or fatal cardiac adverse events, as well as for hypersensitivity reactions, neutropenia, thrombocytopenia, embryo-fetal toxicity, and interference with cross-matching or red blood cell antibody screening. This combination is not recommended for patients with NYHA class IIIB/IV cardiac disease or Mayo stage IIIB disease outside of controlled clinical trials.
Source:
US Food and Drug Administration. Accessed on November 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-daratumumab-and-hyaluronidase-fihj-newly-diagnosed-light-chain
