Efficacy of venetoclax in the treatment of relapsed/refractory light-chain amyloidosis

Few studies have reported that venetoclax, a selective BCL2 inhibitor, has shown promising efficacy in relapsed/refractory AL amyloidosis (RRAL), especially among patients harboring t(11;14). We retrospectively reviewed 29 RRAL patients treated with venetoclax between July 2022 and January 2025. Treatment was given for suboptimal prior response (45%), hematologic progression (38%), or rising involved free light chain not meeting progression criteria (17%). Venetoclax induced rapid and deep responses: 79% achieved very good partial response (VGPR) or complete response (CR), and 52% achieved stringent FLC response. High t(11;14) (> 10%) patients achieved ≥ VGPR in 91% versus 33% in low t(11;14) (p = 0.008). Cardiac responses occurred in 59% of evaluable patients. At a median follow-up of 19.7 months, one-year overall survival and event-free survival were 96.6% and 82.6%, respectively; two deaths were due to cardiac progression. Venetoclax was well tolerated, with mostly grade 1-2 adverse events, except one grade 3 leukopenia/neutropenia with grade 3 infection. These results support venetoclax as an effective and safe therapy for RRAL, particularly in t(11;14) patients, and highlight the need for prospective studies to refine patient selection and optimize treatment strategies.