https://orcid.org/0000-0003-2572-7831
Key Points
Baseline FLC burden does not affect the depth of response in patients with newly diagnosed AL amyloidosis treated with DaraCyBorD
We find limitations of the Mayo 2012 staging system in the era of bortezomib and daratumumab-based therapies
A difference between involved and uninvolved free light chain (dFLC) equal or higher than 180 mg/L is part of the 2012 Mayo staging system for AL amyloidosis given its negative impact on overall survival. However, none of the 758 patients evaluated to develop and validate this staging system received bortezomib or daratumumab-containing regimens. Over the past two decades, cyclophosphamide-bortezomib-dexamethasone (CyBorD) and, more recently, daratumumab-CyBorD (DaraCyBorD) have become cornerstone treatments for AL amyloidosis, demonstrating high efficacy in rapidly normalizing FLC levels. We hypothesized that in newly diagnosed AL amyloidosis patients treated with bortezomib and daratumumab-based regimens, a baseline high free light chain burden may no longer predict adverse prognosis. In this retrospective, multicenter study of 223 newly diagnosed AL amyloidosis patients treated with CyBorD or DaraCyBorD therapy, we investigated: 1) the association between baseline involved FLC (iFLC) and dFLC hematological response at 28 days and 3, 6, 9 and 12 months following commencement of therapy ; 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 prognostic value of bone marrow plasma cell burden in determining response to CyBorD or DaraCyBorD therapy and overall survival; and finally, the prognostic value of the 2012 Mayo staging system in the CyBorD and DaraCyBorD cohorts. Our findings suggest that a dFLC over 180 mg/L no longer holds prognostic value in the era of CyBorD/DaraCyBorD-based AL amyloidosis therapy and question the utility of the Mayo 2012 staging system in the era of highly effective chemo-immunotherapies.
