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

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.