An Evaluation of Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis

The deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells characterizes systemic immunoglobulin light-chain amyloidosis (AL). Recognizing the potential to improve outcomes for this disease with daratumumab, a human CD38-targeting antibody, Kastritis and colleagues randomly assigned patients with newly diagnosed AL to a control group that received 6 cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or to a daratumumab group that was treated with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). A hematologic complete response (CR) was the primary end point.

Undergoing randomization were a total of 388 patients. The median follow-up was nearly 1 year (11.4 months). A hematologic CR was significantly higher in the daratumumab group than in the control group, as marked by the percentage of patients (53.3% compared with 18.1%). The daratumumab group had a survival free from major organ deterioration or hematologic progression that was favored (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% confidence interval, 0.36-0.93; P = .02). In the daratumumab group, at 6 months, more cardiac and renal responses occurred than in the control group, 41.5% compared with 22.2% and 53.0% compared with 23.9%, respectively. The 4 most common grade 3 or 4 adverse events were cardiac failure (6.2% and 4.8%), diarrhea (5.7% and 3.7%), lymphopenia (13.0% and 10%), and pneumonia (7.8% and 4.3%) in the daratumumab group and control group, respectively. In 7.3% of the patients, systemic administration-related reactions to daratumumab arose. A total of 56 patients died primarily due to amyloidosis-related cardiomyopathy (27 patients in the daratumumab group and 29 patients in the control group).

The investigators concluded that the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone treatment was correlated with higher frequencies of hematologic CR and survival free from major organ deterioration or hematologic progression among patients with newly diagnosed AL.

Source: Kastritis E, Palladini G, Minnema MC, et al. Daratumumab-based treatment for immunoglobulin light-chain amyloidosis. N Engl J Med. 2021;385:46-58.

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