The Food and Drug Administration (FDA) has granted accelerated approval for Darzalex Faspro® (daratumumab and hyaluronidase-fihj; Janssen), in combination with bortezomib, cyclophosphamide, and dexamethasone (VCd) for the treatment of adults with newly diagnosed light chain (AL) amyloidosis.
The approval was based on data from the open-label, active-controlled phase 3 ANDROMEDA study that evaluated the efficacy and safety of Darzalex Faspro in combination with VCd in 388 adults with newly diagnosed AL amyloidosis. Patients were randomized 1:1 to receive Darzalex Faspro plus VCd or VCd alone. The primary end point was the proportion of patients with overall complete hematologic response. Results showed that a significantly greater proportion of patients treated with Darzalex Faspro plus VCd achieved hematologic complete response compared with those treated with VCd alone (42% [n=82] vs 13% [n=26]; P <.0001).
As for safety, the most common adverse reactions reported in the Darzalex Faspro plus VCd treatment arm (incidence of greater than or equal to 20%) included upper respiratory tract infection, diarrhea, peripheral edema, constipation, fatigue, peripheral sensory neuropathy, nausea, insomnia, dyspnea and cough. Serious cardiac disorders and fatal cardiac disorders occurred in 16% and 10% of patients treated with the combination therapy, respectively; patients with cardiac involvement of AL amyloidosis should be monitored more frequently for cardiac adverse reactions.
Continued approval of Darzalex Faspro in combination with VCd for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Darzalex Faspro is not indicated and is not recommended for the treatment of patients with AL amyloidosis who have NYHA Class IIIB or Class IV cardiac disease or Mayo Stage IIIB outside of controlled clinical trials.
1. Genmab announces that Janssen has been granted U.S. FDA approval for Darzalex Faspro® (daratumumab and hyaluronidase-fihj) for patients with newly diagnosed light-chain (AL) amyloidosis. [press release]. Copenhagen, Denmark: Genmab A/S; January 15, 2021.
2. Darzalex Faspro [package insert]. Horsham, PA: Janssen Biotech, Inc.; 2021.