High efficacy and tolerability of daratumumab-based regimens in first-line treatment of patients with immunoglobulin light-chain amyloidosis: a real-world evidence analysis

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.