Immunotherapy for the treatment of multiple myeloma

Abstract

Despite advances in treatment for multiple myeloma, the majority of patients ultimately develop relapsed disease marked by immune evasion and resistance to standard therapy. Immunotherapy has emerged as a powerful tool for tumor-directed cytotoxicity with the unique potential to induce immune memory to reduce the risk of relapse. Understanding the specific mechanisms of immune dysregulation and dysfunction in advanced myeloma is critical to the development of further therapies that produce a durable response. Adoptive cellular therapy, most strikingly CAR T cell therapy, has demonstrated dramatic responses in the setting of refractory disease. Understanding the factors that contribute to immune evasion and the mechanisms of response and resistance to therapy will be critical to developing the next generation of adoptive cellular therapies, informing novel combination therapy, and determining the optimal time to incorporate immune therapy in the treatment of myeloma.

DIS3 ribonuclease prevents the cytoplasmic accumulation of lncRNAs carrying non-canonical ORFs, which represent a source of cancer immunopeptides.

“…Currently, some of chimeric antigen receptor (CAR)-T cell therapies and vaccines using peptides are being tested in clinical trials and being used in MM treatments, especially for patients with relapse or refractory cancer 57 . However, there is still need for further development of combinatorial antigen approaches for more e cient and speci c therapies.…”

DIS3 ribonuclease prevents the cytoplasmic accumulation of lncRNAs carrying non-canonical ORFs.

“…Currently, some of chimeric antigen receptor (CAR)-T cell therapies and vaccines using peptides are being tested in clinical trials and being used in MM treatments, especially for patients with relapse or refractory cancer 88 . However, there is still need for further development of combinatorial antigen approaches for more e cient and speci c therapies.…”

Past, Present, and a Glance into the Future of Multiple Myeloma Treatment

“…Stromal-cell-induced MM growth was abrogated by blocking PD1/PD-L1 and enhanced in combination with lenalidomide ex vivo [ 149 ]. Durvalumab and nivolumab, PD-1 inhibitors, are being tested in combination with other compounds such as IMiDs, daratumumab, and venetoclax (Bcl-2 inhibitor) [ 118 , 150 ]. A phase Ib KEYNOTE-013 trial (NCT01953692) for pembrolizumab, a PD-1 inhibitor, in RRMM patients showed 2.7 months PFS and 20.2 months OS after a median follow-up of 19.9 months [ 151 ].…”