Attenuated prognostic discrimination among Mayo stages I–IIIa and improved survival in stage IIIb in the daratumumab era: a real-world study of newly diagnosed AL amyloidosis

Daratumumab-based regimens have become first-line therapy for immunoglobulin light-chain (AL) amyloidosis, but real-world evidence remains limited. In this retrospective study of 265 newly diagnosed patients, daratumumab-based regimens induced rapid hematologic responses, progressive organ responses, and favorable survival outcomes. Survival improved even in stage IIIb disease, with a median overall survival (OS) of 26.2 months, whereas prognostic discrimination among Mayo stage I-IIIa patients was attenuated. Landmark analyses showed that hematologic ≥ very good partial response and cardiac ≥ partial response at 3 months were associated with superior OS. Hematologic complete response predicted improved hematologic event-free survival across all landmark time points, and minimal residual disease negativity at 12 months provided additional prognostic stratification, including among patients who had already achieved hematologic complete response. Patients with t(11;14) showed delayed deep hematologic responses. These findings support the real-world efficacy of daratumumab-based regimens in newly diagnosed AL amyloidosis.