Intravenous daratumumab-based regimens for light-chain amyloidosis with kidney involvement: a retrospective real-world comparative study

Daratumumab (Dara)-based regimens have demonstrated efficacy in AL amyloidosis. However, real-world treatment strategies may differ from the standard Dara-CyBorD regimen because of variations in drug availability and clinical practice. This study compared intravenous daratumumab-based regimens with cyclophosphamide-bortezomib-dexamethasone (CyBorD) in patients with kidney involvement. Patients initially treated with intravenous daratumumab-based regimens or CyBorD were retrospectively included. Treatment efficacy, safety and factors associated with treatment response were analyzed. Ninety-three patients were included, with 30 patients in the Daratumumab group and 63 patients in the CyBorD group. After a median follow-up of 29.8 months in the Daratumumab group and 32.4 months in the CyBorD group, the proportion of patients achieving hematologic very good partial response or better was 83.3% in the Daratumumab group and 65.1% in the CyBorD group, showing a trend toward deeper hematologic responses with daratumumab that did not reach statistical significance ( p = 0.056). Rates of renal partial response or better (63.3% vs. 52.4%, p = 0.320), renal progression (23.3% vs. 30.2%, p = 0.496), and overall survival did not differ significantly between groups. The Daratumumab group had fewer hematologic toxicities, infections, and neuropathy, but two infusion reactions were reported. Multivariable logistic regression revealed that achieving hematologic partial response at one month (OR 2.885, 95% CI 1.029–8.088, p = 0.044) and higher baseline eGFR (OR 1.023, 95% CI 1.001–1.045, p = 0.039) were independently associated with achieving hematologic very good partial response or better. Hematologic complete response (OR 10.600, 95% CI 3.526–31.868, p < 0.001) and history of diabetes (OR 0.067, 95% CI 0.006–0.720, p = 0.026) were independently associated with renal partial response or better. Intravenous daratumumab-based regimens showed comparable clinical outcomes to CyBorD with a favorable tolerability profile in patients with AL amyloidosis and kidney involvement in this real-world study. However, no statistically significant differences in hematologic response, renal response, or survival were detected compared with CyBorD.