Early dflc response for predicting complete hematological response in patients with AL amyloidosis: A multi-center prospective observational study

Abstract Introduction The treatment of AL amyloidosis primarily relies on anti-plasma cell therapy and supportive care. Daratumumab, bortezomib, cyclophosphamide, and dexamethasone (Dara-CyborD) are the standard first-line treatment and have been shown to achieve a complete hematologic response (CHR) in nearly 60% of patients. An early achievement of a CHR is particularly crucial in patients with advanced organ involvement. International Society of Amyloidosis recommended that treatment change should be considered if less than partial hematological response after two cycles or very good partial response after three cycles. Our retrospective study has shown that the earlier differences between free light chain (dFLC) response can predict CHR. To validate this hypothesis, we are conducting a multi-center prospective observational study in China. Methods This ongoing prospective and observational study enrolled patients who all received Dara-CyborD or daratumumab, bortezomib, dexamethasone and had an evaluable dFLC value of more than 50 mg/L. Active myeloma was excluded. All patients received dFLC examination after one week and once a month until CHR. Results As of April 30, 2025, 43 patients were enrolled. This ensures that all patients have at least three months of follow-up. The median age was 66 years (range, 40-90). The cases in Mayo 2004 stage 1/2/3a/3b were 11/10/18/4, respectively, and the cases in Mayo 2012 stage 1/2/3/4 were 8/11/10/14. 32 (74.4%) patients had cardiac involvement. The median dFLC level at baseline was 219.5 mg/L (range, 53.04-1850.30), and 25 of 43 patients had dFLC levels greater than 180 mg/L. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal threshold for the dFLC reduction after one week and after cycle one treatment, which best predicts the hematological complete response within six cycles of treatment. ROC curve analyses revealed that an optimum cut-off point of dFLC reduction ≥ 73% after one week is an effective biomarker for CHR (AUC 0.809, sensitivity 0.759, specificity 0.833, p = 0.002). In addition, dFLC reduction after one cycle of ≥ 90.1% also demonstrated excellent predictive performance to predict CHR (AUC 0.876, sensitivity 0.862, specificity 0.833, p < 0.001). Conclusions In conclusion, our study demonstrates that profound dFLC reduction after one week and after one cycle indicates a high likelihood of CHR, potentially allowing for early modifications of therapy in selected patients, i.e., BCMA bispecific antibody and Bcl-2 inhibitor.