FDA approves daratumumab-hyaluronidase (Darzalex Faspro) combined with VCd for new diagnosis of light chain amyloidosis

On November 19, 2025, the U.S. Food and Drug Administration (FDA) approved daratumumab-hyaluronidase (Darzalex Faspro, manufacturer: Gensan Biotechnology) in combination with bortezomib, cyclophosphamide (Cyclophosphamide) and dexamethasone (VCd) for the treatment of patients with newly diagnosed light chain (AL) amyloidosis. This approval is a traditional approval after the FDA granted accelerated approval for this indication in 2021, marking an important progress in the field of amyloidosis treatment.

1. Background and overview of amyloidosis

Amyloidosis is a systemic disease caused by abnormal protein deposition, of which light chain amyloidosis (AL amyloidosis) is the most common type. The disease is usually caused by the deposition of abnormal light chain proteins produced by plasma cells in the bone marrow in multiple organs, affecting vital organs such as the heart, kidneys, nerves and gastrointestinal tract, leading to organ failure. Due to the severity and multi-organ impact of this condition, early diagnosis and effective treatment are crucial.

2. ANDROMEDA study: clinical data supports FDA approval

The approval of daratumumab-hyaluronidase was based on clinical data from the ANDROMEDA trial (NCT03201965). This is an open-label, randomized, active-controlled phase III trial designed to evaluate the efficacy of standard treatment (VCd) or daratumumab-hyaluronidase plus VCd (D-VCd) in 388 patients with newly diagnosed AL amyloidosis.

In this study, patients were evaluated for major organ progression-free survival (MOD-PFS), which is defined as the duration from the date of randomization to hematological progression, major organ deterioration, or death. After a median follow-up of 61.4 months, the results showed that the MOD-PFS of the D-VCd group was significantly better than that of the VCd group. The specific data are as follows:

1) MOD-PFS in the VCd group did not reach the median;

2) MOD-PFS of D-VCd group was 30.2 months;

3) D-hazard ratio (HR) was 0.47, 95%CI, 0.33-0.67, p value <0.0001, indicating that the risk of disease progression in the D-VCd group was significantly lower.

In addition,The D-VCd group also showed certain advantages in **overall survival (OS)**: the HR of the D-VCd group was 0.63 (95% CI: 0.42, 0.90), and the p value was 0.0121, showing a survival benefit. However, median OS was not reached in either group.

These results indicate that daratumumab-hyaluronidase combination therapy significantly delays disease progression and may improve overall survival in patients with newly diagnosed AL amyloidosis.

3. Treatment options and dosage recommendations

When Daratumumab-hyaluronidase is used in combination with VCd, the recommended dose is: Daratumumab-hyaluronidase: 1800 mg, each injection is used in combination with VCd, subcutaneously.

VCd treatment regimen: includes bortezomib (twice weekly), cyclophosphamide (once weekly), and dexamethasone (once weekly).

Treatment should be carried out according to the recommended schedule, with injections taking approximately 3 to 5 minutes. Through this program, patients can receive treatment in a shorter period of time while achieving longer-term disease control.

4. Safety and Side Effects

Although daratumumab-hyaluronidase has shown efficacy in the treatment of AL amyloidosis, the FDA requires a cardiotoxicity warning to be included in its prescribing information. Serious or fatal cardiac adverse reactions may occur in patients receiving daratumumab-hyaluronidase during treatment, especially in patients with impaired cardiac function.

Other common side effects include allergic reactions, thrombocytopenia, neutropenia, and embryo-fetotoxicity. In addition, cross-matching and interference with red blood cell antibody screening are risks that require special attention.

daratumumab-Hyaluronidase is not indicated for use in patients with NYHA Class IIIb or IV heart disease, or in patients with Mayo Class IIIb heart disease.

Keyword tags:

FDA approval, daratumumab-hyaluronidase, AL amyloidosis, ANDROMEDA study, light chain amyloidosis, cardiotoxicity, biologics, disease progression, overall survival, treatment options

Reference: Updated November 19, 2025, https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-daratumumab-and-hyaluronidase-fihj-newly-diagnosed-light-chain