Venetoclax in Relapse/Refractory AL Amyloidosis—A Multicenter International Retrospective Real-World Study

SIMPLE SUMMARY: Light-chain amyloidosis is a rare disease, and treatment for relapsed light-chain amyloidosis patients is an unmet need. Venetoclax is an oral medication that has proven great efficacy in many hematological cancers, including multiple myeloma. Venetoclax is considered a promising agent for the treatment of relapsed light-chain amyloidosis. We aimed to report the outcomes of therapy in 26 relapsed light-chain amyloidosis patients treated with venetoclax. We found a very high response rate (88%), and most responses were deep and prolonged. Treatment was effective even when doses were reduced. Venetoclax treatment was safe, and one patient died due to infection. These promising results require confirmation in a randomized trial. ABSTRACT: Therapeutic options in relapsed refractory (R/R) light-chain (AL) amyloidosis patients are limited. Given the encouraging results in t(11;14) multiple myeloma and the high prevalence of t(11;14) in AL amyloidosis, venetoclax is an attractive treatment option in this setting. We report here the results of a multi-center retrospective study on 26 R/R AL amyloidosis patients treated off-label with venetoclax. The median lines of therapy prior to venetoclax was 3.5 (range 1–7), and 88% of our cohort had t (11;14). Twenty-two patients (85%) were previously treated with daratumumab. The overall hematologic response rate was 88%, 35% achieved a CR, and 35% achieved VGPR. The median event-free survival was 25 months (m) (95% CI 9.7 m-not reached), and the median overall survival was 33 m (95% CI 25.9–39.2 m). Most of the patients in this cohort are in ongoing deep responses and continuing venetoclax therapy. The treatment was relatively safe. One patient died due to infection, and there were two grade 3 infections in our cohort. Tumor lysis syndrome (TLS) was not seen in any patient. Dose reductions were frequent but did not affect the efficacy. These promising results require confirmation in a randomized controlled trial.