AL Amyloidosis: Current Treatment and Outcomes

Light chain AL amyloidosis is a systemic disorder involving tissue deposition of amyloid fibrils. Often delayed in diagnosis due to nonspecific systemic symptoms, AL amyloidosis must be confirmed on tissue biopsy. Once diagnosis is made, patients can be risk stratified based on the degree of organ involvement and high-risk cytogenetic features. Currently, the only FDA-approved first-line therapy for AL amyloidosis is a combination regimen of daratumumab, cyclophosphamide, bortezomib, and dexamethasone (DaraCyborD) with a goal of achieving a very good partial response (VGPR) after 4-6 cycles of treatment. Autologous stem cell transplant can be considered in selected cases, although there is no robust evidence of superiority over chemotherapy alone. In the relapsed/refractory setting, numerous promising therapies are still under investigation including venetoclax especially for patients with translocation t (11; 14) and chimeric antigen receptor T-cell therapy (CART) targeting B-cell maturation antigen (BCMA). Trial Registration: ClinicalTrials.gov identifier: NCT04270175, NCT05451771, NCT04847453, and NCT05199337.