Plasma Cell precursor and Other Disorders

Category: Plasma Cell precursor and Other Disorders

Early venetoclax salvage in systemic light chain amyloidosis; a retrospective case series

(PA-361) Early Venetoclax Salvage in Systemic Light Chain Amyloidosis; A Retrospective Case Series

Friday, September 19, 2025

Nicholas L. McVilly, MBBS

Haematology registrar
Princess Alexandra Hospital

Introduction: Systemic light chain (AL) amyloidosis is a rare plasma cell disorder characterized by tissue deposition of misfolded light chains, causing progressive organ damage. The chromosomal translocation t(11;14) is present in approximately 50% of AL amyloidosis patients, compared to about 10% in multiple myeloma, and is associated with suboptimal response to first-line bortezomib therapy. Venetoclax, a selective BCL2 inhibitor, has shown efficacy in t(11;14)-positive hematologic malignancies, including myeloma and AL amyloidosis. Early and rapid reduction of light chains is crucial to achieve organ response and prevent disease progression and related morbidity and mortality.

Methods:   We retrospectively reviewed a database from a quaternary amyloidosis referral centre to identify patients treated with venetoclax-based salvage therapy. Baseline characteristics and response assessments were confirmed through detailed chart review, including electronic medical records, laboratory, and imaging data.

Results:   Seven systemic AL amyloidosis patients treated with venetoclax monotherapy or venetoclax plus daratumumab for inadequate initial response were identified. All patients had ≥10% bone marrow plasmacytosis on initial bone marrow biopsy, with a mean of 18.5%. Median dFLC at diagnosis was 82mg/L, with an interquartile range of 382mg/L. All received first-line bortezomib, cyclophosphamide, and dexamethasone; 3 also received daratumumab. The mean age at diagnosis was 62.7 years, with 57% female. Cardiac involvement was present in 6 (86%), and 4 (57%) advanced Mayo 2004 stage III. Venetoclax was dosed at 400 mg daily, or 50 mg with concurrent azole antifungal therapy. To date, patients have received between 4 and 13 monthly cycles of venetoclax (median of 10.5). Hematologic response rate including CR and VGPR was 71% (5/7 patients), with partial response (PR) achieved in the remaining 2 patients. All CRs occurred in patients who began venetoclax within six months of diagnosis due to suboptimal response. Organ responses were observed in 4 patients (57%), including cardiac and renal improvements, even among those without hematologic CR. Venetoclax was generally well-tolerated; 1 patient experienced grade 3 thrombocytopenia, with no grade 3/4 neutropenia, febrile neutropenia or tumour lysis syndrome reported. One patient died due to progressive disease having only achieved a haematological PR.

Conclusions:   Venetoclax is a safe and effective salvage therapy for AL amyloidosis patients with t(11;14), particularly when initiated early after diagnosis. It yields high hematologic and organ response rates, underscoring its potential to improve outcomes in this challenging population. Further studies are warranted to explore its role in frontline therapy and earlier salvage interventions to reduce morbidity and mortality.