BCL2 inhibition for multiple myeloma and AL amyloidosis

Abstract

Despite the development of novel treatments, multiple myeloma (MM) and light-chain (AL) amyloidosis remain incurable diseases. BCL2 inhibitors are a class of drugs under development for plasma cell disorders, with strong data supporting their use, particularly in patients with MM and AL amyloidosis harbouring the t(11;14). Venetoclax, the most extensively studied BCL2-specific inhibitor, was initially designed and evaluated for other malignant blood disorders. However, it has since shown promising efficacy in both randomized and real-world studies for MM and AL amyloidosis, either as a monotherapy or in combination with other agents. Nonetheless, toxicity concerns have been raised, underscoring the need for careful patient selection and precise dose optimization. Additionally, other BCL2-targeting drugs are under investigation in preclinical and clinical studies. This review focuses on the current role of BCL2 inhibitors in the treatment landscape of MM and AL amyloidosis.