High efficacy and tolerability of daratumumab-based regimens in first-line treatment of patients with immunoglobulin light-chain amyloidosis: a real-world evidence analysis
- 1Department of Hematology, The Second Xiangya Hospital, Central South University
Abstract
Background: Daratumumab was the first monoclonal antibody targeting cluster of differentiation 38 (CD38) to demonstrate high response rates in both untreated and pretreated cases of immunoglobulin light-chain (AL) amyloidosis.
Patients and methods: We conducted a single-center, retrospective real-world case series to evaluate the efficacy and safety of daratumumab as a first-line treatment option. Daratumumab was administered with bortezomib and dexamethasone (D-Vd), bortezomib, cyclophosphamide, and dexamethasone (D-VCd), or low-dose dexamethasone (Dd).
Results: Forty-four patients were eligible, including 14 patients with stage IIIb. By the 6-month milestone (N = 36), 21 (59%) patients achieved at least complete response (CR), 10 (28%) patients achieved very good partial response (VGPR), and 5 (14%) patients achieved partial response (PR). The cardiac response rate was 50% at 3 months, 69% at 6 months, and 84% at 12 months. The renal response rate reached 40% by the 6-month mark. Importantly, hematologic, cardiac, and renal response rates were generally comparable between stage IIIb and non-stage IIIb patients. After a median follow-up of 13 (range 2-45) months, 6 (14%) patients died, all with stage IIIb disease. The median overall survival (OS) was not reached, with a 6-month survival rate of 93% and a 1-year survival rate of 84%. Univariate analysis showed that Mayo stage IIIb, difference between involved and uninvolved free light chains (dFLC) ≥ 300 mg/L, and a time to treatment of more than 12 months were associated with poor overall survival. Lymphocytopenia emerged as the most prevalent hematologic adverse effect, with grade 3-4 lymphocytopenia observed in 32% of patients. Among non-hematologic adverse reactions, infection was observed in 39% of patients.
Conclusion: Daratumumab demonstrates significant efficacy in treating newly diagnosed AL amyloidosis, with excellent hematologic and organ response rates, a remarkable safety profile, and favorable tolerability among AL amyloidosis patients. However, early cardiac mortality before responses could manifest underscores that advanced cardiac stage remains an adverse prognostic factor for OS.
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BibTeX
@article{cui2026high,
title = {{High efficacy and tolerability of daratumumab-based regimens in first-line treatment of patients with immunoglobulin light-chain amyloidosis: a real-world evidence analysis}},
author = {Yajuan Cui and Yunya Luo and Ji Li and Lingli Yuan and Zhihua Wang and Hongling Peng and Ruijuan Li},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1960805},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1960805/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - High efficacy and tolerability of daratumumab-based regimens in first-line treatment of patients with immunoglobulin light-chain amyloidosis: a real-world evidence analysis
AU - Yajuan Cui
AU - Yunya Luo
AU - Ji Li
AU - Lingli Yuan
AU - Zhihua Wang
AU - Hongling Peng
AU - Ruijuan Li
PY - 2026
DA - 2026/10/28
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1960805
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1960805/full
AB - Background: Daratumumab was the first monoclonal antibody targeting cluster of differentiation 38 (CD38) to demonstrate high response rates in both untreated and pretreated cases of immunoglobulin light-chain (AL) amyloidosis. Patients and methods: We conducted a single-center, retrospective real-world case series to evaluate the efficacy and safety of daratumumab as a first-line treatment option. Daratumumab was administered with bortezomib and dexamethasone (D-Vd), bortezomib, cyclophosphamide, and dexamethasone (D-VCd), or low-dose dexamethasone (Dd). Results: Forty-four patients were eligible, including 14 patients with stage IIIb. By the 6-month milestone (N = 36), 21 (59%) patients achieved at least complete response (CR), 10 (28%) patients achieved very good partial response (VGPR), and 5 (14%) patients achieved partial response (PR). The cardiac response rate was 50% at 3 months, 69% at 6 months, and 84% at 12 months. The renal response rate reached 40% by the 6-month mark. Importantly, hematologic, cardiac, and renal response rates were generally comparable between stage IIIb and non-stage IIIb patients. After a median follow-up of 13 (range 2-45) months, 6 (14%) patients died, all with stage IIIb disease. The median overall survival (OS) was not reached, with a 6-month survival rate of 93% and a 1-year survival rate of 84%. Univariate analysis showed that Mayo stage IIIb, difference between involved and uninvolved free light chains (dFLC) ≥ 300 mg/L, and a time to treatment of more than 12 months were associated with poor overall survival. Lymphocytopenia emerged as the most prevalent hematologic adverse effect, with grade 3-4 lymphocytopenia observed in 32% of patients. Among non-hematologic adverse reactions, infection was observed in 39% of patients. Conclusion: Daratumumab demonstrates significant efficacy in treating newly diagnosed AL amyloidosis, with excellent hematologic and organ response rates, a remarkable safety profile, and favorable tolerability among AL amyloidosis patients. However, early cardiac mortality before responses could manifest underscores that advanced cardiac stage remains an adverse prognostic factor for OS.
SN - 1664-3224
ER -