Predictive value of free light chain burden in patients with AL amyloidosis treated with bortezomib-based regimens

A difference between involved and uninvolved free light chains (dFLC) ≥180 mg/L is part of the 2012 Mayo staging system for amyloid light chain (AL) amyloidosis given its negative impact on overall survival (OS). However, none of the 758 patients evaluated to develop and validate this staging system received bortezomib or daratumumab-containing regimens. Over the past 2 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 patients with newly diagnosed AL amyloidosis treated with bortezomib- and daratumumab-based regimens, a baseline high FLC burden may no longer predict adverse prognosis. In this retrospective, multicenter study of 223 patients with newly diagnosed AL amyloidosis treated with CyBorD or DaraCyBorD therapy, we investigated (1) the association between baseline involved FLC and dFLC hematologic response at 28 days and 3, 6, 9, and 12 months after the commencement of therapy; (2) the OS of patients with baseline low (<180 mg/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 OS and, finally, the prognostic value of the 2012 Mayo staging system in the CyBorD and DaraCyBorD cohorts. Our findings suggest that a dFLC of >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 chemoimmunotherapies.