Venetoclax in AL amyloidosis- is this the beginning or the end?

Publication date: Available online 15 July 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Vikram Premkumar, Raymond Comenzo, Suzanne LentzschAbstractAL Amyloidosis (AL) is a plasma cell disease marked by production and deposition of toxic free light chains in organs including the heart, kidney and nervous system. While treatment is generally borrowed from multiple myeloma (MM), patients typically have difficulty tolerating many of these drugs, namely the immunomodulatory drugs (IMiDs), due to high cardiac and hematologic toxicities. Recently daratumumab has been shown to be active in (AL), however for patients who become refractory to daratumumab, options remain bleak. Given the relative prevalence of t(11;14) in patients with AL, and subsequent overexpression of BCL-2, we report two cases of deep and durable responses to treatment with venetoclax in combination with a proteasome inhibitor. Recently the FDA has put a hold on studying venetoclax in MM given the results of the BELLINI trial (NCT02755597) examining the efficacy of venetoclax in MM. Preliminary results indicate an increased rate of death in the venetoclax arm when compared to placebo, largely due to infection. We hope that with proper infectious prophylaxis we can abrogate the perceived increased rate of death and the hold on venetoclax can be lifted. Given the high quality and durable responses seen in these cases we believe venetoclax warrants further study in AL.
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research