Options for Rescue Treatment of Patients with AL Amyloidosis Exposed to Upfront Daratumumab

This review aims to assess the therapeutic strategies available for relapsed/refractory patients with immunoglobulin light chain (AL) amyloidosis who received upfront daratumumab-based regimens.

The treatment landscape of AL amyloidosis has changed radically thanks to the introduction in the upfront setting of daratumumab in combination with bortezomib, cyclophosphamide and dexamethasone (DaraCyBorD) which improved patients’ outcomes increasing the rate of hematologic and organ responses. However, many patients eventually relapse or are refractory to daratumumab and the best salvage therapy is not well defined yet. In this contest, we reviewed the available therapeutic options after daratumumab failure, and we look towards the current advances in Bcl-2 inhibitors, novel immunotherapeutic agents as chimeric antigen receptor (CAR-T) therapy and bispecific antibodies (bsAbs).

Relapsed/refractory AL amyloidosis represent an unmet clinical need and novel targeted drugs require urgent prospective assessment.