Daratumumab and bortezomib, the first-line drugs for AL amyloidosis, typically yield a complete hematologic response (CHR) rate of nearly 60% when used in combinations. An early achievement of CHR is crucial in amyloidosis. We retrospectively evaluated the relationship between dFLC (the difference between free light chain) reduction by Day 7 in Cycle 1 (C1D7) and CHR, organ response, and survival in 48 newly diagnosed AL amyloidosis patients receiving daratumumab, bortezomib, and dexamethasone. The CHR rate within six months was 66.7%. Using Receiver Operating Characteristic Curve curve analysis, we predicted CHR based on a dFLC reduction in C1D7 (67.0% change, optimal sensitivity 87.5%, specificity 81.3%). We introduce the novel concept of "rapid hematologic dFLC response", defined as a reduction in dFLC levels ≥ 67% in C1D7. The CHR rate in rapid responders' groups was higher than that in slow responders' group (90.3% vs. 23.5%, P<
0.01). After a median follow-up of 19 months (range: 0.3-57), the renal response rate in rapid responders was higher than that in slow responders (72.0% vs. 27.5%, P = 0.025). The median major organ deterioration event-free survival in the rapid responders' group (not reached) was significantly superior to that in the slow responders' group (19 m, 95% CI: 1.79-23.14 m, P = 0.048). In conclusion, early dFLC reduction in C1D7 indicates a high possibility of CHR and organ response and may allow for early modification of therapy in selected patients.