Key result
Daratumumab-CyBorD provided an overall survival advantage over CyBorD alone in previously untreated AL amyloidosis, with an absolute improvement of ~12% at 5 years despite substantial crossover.
Why the study?
Does daratumumab-CyBorD improve overall survival in previously untreated systemic AL amyloidosis compared to CyBorD alone?
Does daratumumab-CyBorD improve overall survival in previously untreated systemic AL amyloidosis compared to CyBorD alone?
Answers are grounded in this paper and cite their sources.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The final analysis of the ANDROMEDA trial marks a landmark moment in AL amyloidosis: confirming that rapid and profound hematologic responses, driven by combining anti-CD38 monoclonal antibody daratumumab with CyBorD, translates into a clinically meaningful survival benefit. Daratumumab now joins melphalan and bortezomib as the third agent in AL to improve OS in a randomized trial.”
“In ANDROMEDA, the cardiac CR rate was approximately threefold higher with daratumumab-CyBorD than CyBorD alone (40.7% vs 13.7%), and patients achieving cardiac CR demonstrated a near-flat survival curve with 5-year OS exceeding 95%.”
“Cardiac treatment-emergent adverse events (TEAEs) were substantial: 9.3% of patients experienced cardiac failure and 11.4% of patients in the daratumumab-CyBorD arm died due to adverse events within 30 days of the last study treatment, although most were attributed to baseline cardiac involvement rather than treatment.”
The addition of daratumumab to CyBorD in previously untreated AL amyloidosis provides a clinically meaningful long-term overall survival benefit.
In this issue of Blood, Kastritis et al 1 report the final analysis of the ANDROMEDA trial, which compared daratumumab-CyBorD (cyclophosphamide, bortezomib, and dexamethasone) vs CyBorD alone in previously untreated systemic immunoglobulin light chain (AL) amyloidosis.The initial 2021 report established a threefold improvement in hematologic complete response (heme-CR) with daratumumab-CyBorD 2 ; the final analysis now confirms that this improvement in deep hematologic response translates into a clinically meaningful overall survival (OS) advantage, an absolute improvement of ~12% in 5 years. 1 Strikingly, this survival benefit emerged despite substantial crossover with 71% of patients in the control arm receiving a daratumumab-based regimen as subsequent therapy.
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Rajshekhar Chakraborty (2026) conducted an editorial in previously untreated systemic immunoglobulin light chain (AL) amyloidosis. daratumumab-CyBorD vs. CyBorD alone was evaluated on overall survival (OS). Daratumumab-CyBorD provided an overall survival advantage over CyBorD alone in previously untreated AL amyloidosis, with an absolute improvement of ~12% at 5 years despite substantial crossover.
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