Frontline therapy for systemic light chain (AL) amyloidosis has evolved significantly with the approval of daratumumab in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCD), which has significantly improved rates of both hematologic and organ responses. Despite these advances, many patients eventually relapse, and there remains no established standard salvage regimen or optimal timing. In this review, we examine optimal timing of salvage regimens and currently available therapeutic options following daratumumab failure, including next generation proteosome inhibitors or immunomodulatory drugs, autologous stem cell transplant, BCL-2 inhibitors and emerging immunotherapeutic agents such as chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies).
Ling et al. (2026) studied this question.