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October 17, 2025Open Access

Profound dFLC decrease after one cycle predicts superior outcome in patients with AL amyloidosis

Key Points

Profound decrease in dFLC after one cycle predicts high complete hematologic response rates in AL amyloidosis patients.
Patients with >87% dFLC reduction had a 90.5% rate of complete hematologic response versus 43.5% in those with lower reductions.
ROC analysis identified dFLC reduction as a significant predictor of treatment response post one cycle of therapy.
Early identification of optimal responders supports potential early treatment modifications for better patient outcomes.

Abstract

The relationship between an early decrease in the difference between involved and uninvolved free light chains (dFLC) and clinical outcomes in AL amyloidosis is significant. We conducted a multicenter study (n = 86, baseline dFLC ≥ 50 mg/L) in which all patients received frontline daratumumab-bortezomib therapy. ROC analysis identified a dFLC reduction after one cycle (87% reduction, AUC = 0.82) as predictive of complete hematologic response (CHR). Patients achieving >87% dFLC or a very good partial response after one cycle were classified as optimal responders (O-HR), while those who did not were classified as suboptimal response (S-HR). The O-HR group had higher rate of CHR (90.5% vs. 43.5%, p < 0.001), cardiac response (68.9% vs. 36.8%, p = 0.017), and renal response (76.6% vs. 50.0%, p = 0.045) than the S-HR group. Profound dFLC decrease after one cycle suggests high CHR and organ response likelihood, supporting early treatment modification.

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