Predictive Value of Free Light Chain Burden in Patients Newly Diagnosed with AL Amyloidosis Treated with Cybord or Daracybord

Background: A difference between involved and non-involved free light chain (dFLC) exceeding 180 mg/L is part of the 2012 Mayo staging system. However, none of the 758 patients evaluated to develop this staging system received a bortezomib-containing regimen. We hypothesized that depth of response and overall survival in AL amyloidosis patients are independent of free light chain burden in the era of CyBorD and DaraCyBorD. Methods: This is a retrospective, multicentre study including 223 newly diagnosed AL amyloidosis patients seen at our institutions between 2012 and 2024. In patient cohorts receiving CyBorD or DaraCyBorD therapy, we investigated 1) the relationship between baseline iFLC and dFLC at completion of cycle 1 (day 28) and 3, 6, 9 and 12 months ; 2) the overall survival of patients with baseline low (<180mg/L), medium (180-400 mg/L) and high (>400 mg/L) dFLC ; and 3) the validity of the 2004 and 2012 Mayo staging guidelines. The study was IRB approved. Results: We identified 132 patients treated with CyBorD and 91 treated with DaraCyBorD. Forty patients in the CyBorD cohort and 3 in the DaraCyBorD cohort did not respond to therapy. Lack of response was independent of baseline iFLC. Following completion of cycle 1, we identified no correlation (r2=0.02) between baseline iFLC and dFLC response in the DaraCyBorD group and a moderate correlation (r2=0.53) in the CyBorD group. Similar trends were noted at 3, 6, 9 and 12 months from therapy start. Kaplan-Meier survival curves based on baseline iFLC were overlapping with a median follow up of 12.5 months. Mayo 2012 staging did not impact OS. Conclusion: Overall survival, depth and rapidity of response appear to be independent from baseline iFLC in patients treated with bortezomib containing regimens. Our data questions the prognostic impact of free light chain burden in the era of CyBorD and DaraCyBorD.