BACKGROUNDSystemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease. METHODSWe randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response. RESULTSA total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage of patients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53.3% vs. 18.1%) (relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1; P<0.001). Survival free from major organ deterioration or hematologic progression favored the daratumumab group (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to 0.93; P = 0.02). At 6 months, more cardiac and renal responses occurred in the daratumumab group than in the control group (41.5% vs. 22.2% and 53.0% vs. 23.9%, respectively). The four most common grade 3 or 4 adverse events were lymphopenia (13.0% in the daratumumab group and 10.1% in the control group), pneumonia (7.8% and 4.3%, respectively), cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7%). Systemic administration-related reactions to daratumumab occurred in 7.3% of the patients. A total of 56 patients died (27 in the daratumumab group and 29 in the control group), most due to amyloidosis-related cardiomyopathy. CONCLUSIONSAmong patients with newly diagnosed AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression. (Funded by Janssen Research and Development; ANDROMEDA ClinicalTrials.gov number, NCT03201965.

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In the phase 3 ANDROMEDA trial, patients treated with daratumumab, bortezomib, cyclophosphamide, and dexamethasone (D‐VCd) had significantly higher rates of organ and hematologic response compared with patients who received VCd alone. Here, we present patient‐reported outcomes (PROs) from the ANDROMEDA trial. PROs were assessed through cycle 6 using three standardized questionnaires. Treatment effect through cycle 6 was measured by a repeated‐measures, mixed‐effects model. The magnitude of changes in PROs versus baseline was generally low, but between‐group differences favored the D‐VCd group. Results were generally consistent irrespective of hematologic, cardiac, or renal responses. More patients in the D‐VCd group experienced meaningful improvements in PROs; median time to improvement was more rapid in the D‐VCd group versus the VCd group. After cycle 6, patients in the D‐VCd group received daratumumab monotherapy and their PRO assessments continued, with improvements in health‐related quality of life (HRQoL) reported through cycle 19. PROs of subgroups with renal and cardiac involvement were consistent with those of the intent‐to‐treat population. These results demonstrate that the previously reported clinical benefits of D‐VCd were achieved without decrement to patients' HRQoL and provide support of D‐VCd in patients with AL amyloidosis.