Background: Daratumumab is increasingly used in the treatment of light chain (AL) amyloidosis, yet real-world comparative data on its safety and effectiveness remain limited. This study evaluates one-year clinical outcomes between patients with AL amyloidosis treated with daratumumab-based regimens versus those who did not receive daratumumab.

Methods: Using the TriNetX US Collaborative Network, we identified adults diagnosed with AL amyloidosis (ICD-10: E85.81) between January 2021 and June 2024. Patients with stage 3 disease or prior amyloidosis were excluded. Cohort 1 included 738 patients who received daratumumab within 3 months of diagnosis; Cohort 2 included 3,928 patients who did not receive daratumumab. After 1:1 propensity score matching, 692 patients remained in each group. Outcomes assessed over 12 months post-treatment initiation included mortality, heart failure, cardiomyopathy, cardiac arrest, chronic kidney disease (CKD), infections, hematologic adverse events, and neurologic complications.

Results: Mortality at one year was significantly higher in the daratumumab group (21.0% vs. 12.5%; risk ratio [RR] 1.68, p<0.001). Kaplan-Meier survival was also lower in the daratumumab group (78.4% vs. 86.6%, p<0.001). Daratumumab-treated patients had higher rates of heart failure (30.4% vs. 12.4%; RR 2.46), cardiomyopathy (32.0% vs. 12.1%; RR 2.64), and cardiac arrest or shock (6.7% vs. 2.4%; RR 2.75), all p<0.001. CKD was more frequent in the daratumumab cohort (30.5% vs. 16.6%, RR 1.83, p<0.001), as were infections (18.5% vs. 8.6%, RR 2.14, p<0.001) and hematologic adverse events (30.9% vs. 18.3%, RR 1.69, p<0.001). Neurologic events were also elevated (4.8% vs. 2.4%; RR 1.97, p=0.026). The daratumumab group also had significantly higher rates of stem cell transplants (9.4% vs. 5.3%; RR 1.77, p=0.005)

Conclusions: In this real-world cohort, daratumumab-treated AL amyloidosis patients exhibited significantly higher rates of one-year mortality and major adverse events, including cardiac, renal, infectious, and hematologic complications, compared to matched patients receiving non-daratumumab therapy. These findings highlight the need for careful patient selection and close monitoring when initiating daratumumab in AL amyloidosis and emphasizes the importance of additional prospective safety studies.

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2025
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