FDA Grants Daratumumab Traditional Approval for Newly Diagnosed Light Chain Amyloidosis

The FDA has granted a traditional approval to daratumumab and hyaluronidase-fihj (Darzalex Faspro) with bortezomib (Velcade), cyclophosphamide, and dexamethasone (VCd) for patients with newly diagnosed light chain amyloidosis (AL).¹

In 2021 the FDA granted the combination accelerated approval, based on preliminary data from the ANDROMEDA trial (NCT03201965), which were published at the time in the New England Journal of Medicine (NEJM).^2,3

The traditional approval was based on the latest data from the ANDROMEDA trial. The open-label, randomized, active-controlled trial had a total enrollment of 388 patients.

The primary efficacy data from ANDROMEDA considered by the FDA were major organ deterioration progression-free survival (MOD-PFS) and overall survival (OS). After a median follow-up of 61.4 months, the ANDROMEDA trial demonstrated an improvement in MOD-PFS in the daratumumab and hyaluronidase plus VCd arm vs the VCd alone arm (HR, 0.47; 95% CI, 0.33-0.67; P < .0001).¹ The median MOD-PFS was not reached in the daratumumab and hyaluronidase plus VCd arm compared with 30.2 months in the VCd alone arm.

An improvement in OS was also observed with the addition of daratumumab and hyaluronidase vs VCd alone (HR, 0.62; 95% CI, 0.42-0.90; P = .0121).The median OS had not yet been reached in either arm at the data cutoff.¹

In terms of adverse events (AEs), data from the NEJM article showed that at 6 months, more cardiac and renal responses occurred in the daratumumab and hyaluronidase arm than in the VCd alone group (41.5% vs 22.2%; 53.0% vs 23.9%).³ The most common grade 3 or 4 AEs were lymphopenia (13% vs 10.1%), pneumonia (7.8% vs 4.3%), cardiac failure (6.2% vs 4.8%), and diarrhea (5.7% vs 3.7%).

“The safety profiles of daratumumab and bortezomib, cyclophosphamide, and dexamethasone in this trial were consistent with their known profiles and the underlying disease,” first study author Efstathios Kastritis, MD, et al wrote in their published 2021 NEJM article.³ “As in previous trials of daratumumab involving patients with multiple myeloma, an increase in hematologic [AEs] and infections was observed. Peripheral neuropathy was more frequent in the daratumumab group than in the control group, but the incidence of grade 3 or 4 peripheral sensory neuropathy was low and similar in the 2 groups. In a multisystem disease such as [AL], it may be difficult to differentiate between disease manifestations and treatment-related complications, and [AEs] from multidrug regimens represent a challenge for these patients, who are often frail and have multiorgan involvement.”

According to the FDA, the label for daratumumab and hyaluronidase-fihj includes warnings and precautions for cardiac toxicity, hypersensitivity, neutropenia, thrombocytopenia, embryo-fetal toxicity, and interference with cross-matching and red blood cell antibody screening.¹

The recommended dose of the treatment is 1800 mg of daratumumab with 30,000 units of hyaluronidase-fihj administered subcutaneously into the abdomen over 3 to 5 minutes, according to the recommended schedule in combination with bortezomib, cyclophosphamide, and dexamethasone.

REFERENCES

1. FDA grants traditional approval to daratumumab and hyaluronidase-fihj for newly diagnosed light chain amyloidosis. FDA. Published and accessed November 19, 2025. https://tinyurl.com/3wwuss3j

2. FDA grants accelerated approval to Darazalex Faspro for newly diagnosed light chain amyloidosis. FDA. Published January 15, 2021. Accessed November 19, 2025. https://tinyurl.com/5c7djh7d

3. Kastritis E, Palladini G, Minnema M et al. Daratumumab-based treatment for immunoglobulin light-chain amyloidosis. N Engl J Med. 2021;385:46-58. doi: 10.1056/NEJMoa2028631