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

Area of Science:

• Hematology
• Oncology
• Clinical Research

Background:

• Therapeutic options for relapsed refractory (R/R) light-chain (AL) amyloidosis are limited.
• The t(11;14) genetic translocation is prevalent in AL amyloidosis and associated with positive outcomes in multiple myeloma treated with venetoclax.
• Venetoclax represents a potential targeted therapy for AL amyloidosis, especially in the t(11;14) subgroup.

Purpose of the Study:

• To evaluate the efficacy and safety of off-label venetoclax treatment in patients with relapsed refractory AL amyloidosis.
• To assess hematologic response rates, event-free survival (EFS), and overall survival (OS) in this patient cohort.
• To identify the safety profile, including adverse events like infection and tumor lysis syndrome (TLS).

Main Methods:

• A multi-center retrospective study involving 26 patients with R/R AL amyloidosis.
• Patients received off-label venetoclax, with a median of 3.5 prior lines of therapy.
• Genetic analysis confirmed t(11;14) in 88% of patients; 85% had prior daratumumab treatment.

Main Results:

• An overall hematologic response rate of 88% was observed, with 35% achieving complete remission (CR) and 35% achieving very good partial remission (VGPR).
• Median event-free survival was 25 months, and median overall survival was 33 months.
• The treatment was generally safe, with no cases of tumor lysis syndrome (TLS) and manageable infections; dose reductions were common but did not impair efficacy.

Conclusions:

• Venetoclax demonstrates significant efficacy and a favorable safety profile in heavily pretreated R/R AL amyloidosis patients, particularly those with t(11;14).
• Deep and ongoing responses suggest venetoclax as a promising therapeutic strategy.
• Further validation in a randomized controlled trial is warranted to confirm these findings.