On January 15, the U.S. Food and Drug Administration (FDA) granted accelerated approval to daratumumab plus hyaluronidase-fihj (Darzalex Faspro) in combination with bortezomib, cyclophosphamide, and dexamethasone for newly diagnosed light chain amyloidosis.
Efficacy was evaluated in ANDROMEDA, an open-label, randomized, active-controlled trial in 388 patients with newly diagnosed light chain amyloidosis with measurable disease and at least one affected organ according to consensus criteria. Patients were randomly assigned to receive bortezomib, cyclophosphamide, and dexamethasone (VCd arm), or the combination plus daratumumab plus hyaluronidase-fihj (D-VCd arm).
The hematologic complete response rate based on established consensus response criteria as evaluated by an independent review committee was 42.1% for the D-VCd arm and 13.5% for the VCd arm (odds ratio = 4.8, 95% confidence interval = 2.9–8.1, P < .0001).
The prescribing information includes warnings and precautions that serious or fatal cardiac adverse reactions occurred in patients with light chain amyloidosis who received daratumumab plus hyaluronidase-fihj in combination with bortezomib, cyclophosphamide, and dexamethasone. Daratumumab plus hyaluronidase-fihj is not indicated and is not recommended for the treatment of patients with light chain amyloidosis who have New York Heart Association class IIIB or class IV cardiac disease, or Mayo stage IIIB, outside of controlled clinical trials.
The most common adverse reactions (≥ 20%) in patients with light chain amyloidosis who received the D-VCd regimen were upper respiratory tract infection, diarrhea, peripheral edema, constipation, peripheral sensory neuropathy, fatigue, nausea, insomnia, dyspnea, and cough.
The recommended daratumumab plus hyaluronidase-fihj dose is 1,800 mg of daratumumab and 30,000 units of hyaluronidase-fihj administered subcutaneously into the abdomen over approximately 3 to 5 minutes, according to the recommended schedule in combination with VCd.