The combination of daratumumab and hyaluronidase-fihj and bortezomib, cyclophosphamide, and dexamethasone (D-VCd) was granted accelerated approval for the treatment of adults with newly diagnosed light chain (AL) amyloidosis. This approval makes daratumumab and hyaluronidase-fihj the first FDA-approved treatment for patients with this blood cell disorder.
The application was reviewed under the FDA’s Real-Time Oncology Review program, which allows data for certain applications to be reviewed before the applicant formally submits the complete application. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
The FDA’s decision was based on results from the phase III, randomized, open-label ANDROMEDA study that investigated the safety and efficacy of D-VCd, compared with VCd alone, in 388 patients with newly diagnosed AL amyloidosis. Participants who received D-VCd experienced a complete hematologic response rate more than triple that of patients receiving VCd alone: 42% versus 13% (p<0.0001).
The most common AEs (occurring in ≥20% of participants) included upper respiratory tract infection, diarrhea, peripheral edema, constipation, fatigue, and peripheral sensory neuropathy. Serious AEs occurred in 43% of patients who received the daratumumab-based combination, the most common of which were pneumonia (9%), cardiac failure (8%), and sepsis (5%). Fatal AEs occurred in 11% of patients; these included cardiac arrest (4%), sudden death (3%), cardiac failure (3%), and sepsis (1%).
Based on these cardiac toxicities, the FDA noted that this daratumumab-based combination is not indicated and is not recommended for the treatment of patients with AL amyloidosis who have New York Heart Association Class IIIB or Class IV cardiac disease or Mayo Cardiac Stage IIIB disease outside of controlled clinical trials.
Source: Johnson & Johnson press release, January 15, 2021.