Bortezomib-induced immunogenic cell death in myeloma

Kenneth Anderson, MD, Dana-Farber Cancer Institute, Boston, MA, discusses the findings of a study investigating the mode of action of bortezomib, a proteasome inhibitor, in multiple myeloma. Cell culture analyses showed that bortezomib induces immunogenic cell death of myeloma cells. Calreticulin (CALR) was identified as having a critical role in bortezomib-induced immunogenicity. RNAseq experiments were conducted on bortezomib-treated versus untreated tumors and showed that a specific ICD signature was associated with bortezomib use and that increased expression of this signature was strongly correlated with positive clinical outcomes. It was found that bortezomib induced a type-1-interferon ICD response via cGAS/STING pathway activation. STING activation induced potent anti-myeloma activity, suggesting STING agonists may be beneficial in myeloma. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.