Systemic light-chain (AL) amyloidosis is a rare disorder characterized by deposition of misfolded monoclonal immunoglobulin light chains as amyloid fibrils that lead to organ dysfunction. Daratumumab-based regimens have become the frontline therapy. This study evaluates the clinical outcomes and survival of newly diagnosed AL patients treated with daratumumab-containing regimens, representing the largest real-world cohort reported from China to date.

A total of 265 newly diagnosed patients with AL amyloidosis who received daratumumab-based therapy were analyzed. Hematologic, cardiac, renal and hepatic responses were evaluated using a standardized four-tiered classification: complete response (CR), very good partial response (VGPR), partial response (PR), and no response (NR). Fix-time points landmark analysis and longitudinal analyses were used to examine the relationship between responses and survival outcomes.

Among the 265 patients, 67.5% were male, and the median age was 61 years (range, 30-78 years). Cardiac, renal, and hepatic involvement was observed in 90.9%, 49.1%, and 16.6% of patients, respectively. The median baseline N-terminal pro–B-type natriuretic peptide (NT-proBNP) level was 3,830 pg/mL, and the median difference between involved and uninvolved free light chains (dFLC) was 417 mg/L. According to the Mayo 2004 staging system, 8.3%, 45.3%, 25.6%, and 20.8% of patients were classified as stage I, II, IIIa, and IIIb, respectively. Based on the Mayo 2012 staging system, 9.3%, 8.5%, 33.6%, and 38.6% were in stages I, II, III, and IV, respectively.

Hematologic responses at 3 months showed 43.1% CR, 36.5% VGPR and 61.3% stringent FLC response, with an overall response rate (ORR) of 95.4%. The CR rate continued to increase over time, reaching 58.8%, 67.4%, and 75.8% at 6, 12, and 24 months, respectively. Cardiac responses were assessable in 182, 144, 122, and 88 patients at the 3-, 6-, 12-, and 24-month landmarks, respectively. VGPR or better responses were achieved in 10.4%, 27.1%, 44.3%, and 64.8% of patients, respectively. Similar trends were observed in renal and hepatic responses, with VGPR-or-better renal response in 18.9%, 29.5%, 34.9%, and 30.8% of patients, and hepatic VGPR-or-better in 13.3%, 27.3%, 35.3%, and 80.0%, respectively.

The median follow-up time was 23.0 months (interquartile range: 20.8-25.3 months). Two-year overall survival (OS) rates according to the Mayo 2004 stages were 90.9% (stage I), 86.3% (stage II), 75.8% (stage IIIa), and 53.3% (stage IIIb). Notably, the median OS for stage IIIb patients reached 32.8 months (95% CI: 4.6-not reached). No significant difference in OS was observed among patients with stage I, II, and IIIa.

Daratumumab-based therapy improved hematologic and organ responses over time. The median overall survival in stage IIIb improved to 32.8 months. The Mayo 2004 staging system demonstrated limited prognostic discrimination among patients with earlier-stage disease in the context of daratumumab-containing regimens. Traditional markers of monoclonal plasma cell burden, including M-protein level, dFLC, and bone marrow plasma cell percentage, were no longer predictive of survival.

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2025
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