The challenges of checkpoint inhibition in the treatment of multiple myeloma.

Journal Article (Journal Article;Review)

Despite significant improvements in the overall survival of patients with multiple myeloma (MM) over the past 15 years, the disease remains incurable. Treatment options are limited for patients who have relapsed or are refractory to immunomodulatory drugs (IMiDs), proteasome inhibitors, and monoclonal antibodies. In these patients, immunotherapies such as checkpoint inhibitors, oncolytic vaccines, and chimeric antigen receptor (CAR) T cells provide a potentially effective alternative treatment. While checkpoint inhibitors are effective in prolonging overall survival in some patients with advanced solid cancers and Hodgkin lymphoma, they have not demonstrated significant activity as a single agent in MM. In fact the combination of checkpoint inhibitors with IMiDs was recently found to increase the risk of death in myeloma patients. These challenges highlight the need for a better understanding of immune dysregulation in myeloma patients, and the mechanisms of action of- and resistance to- checkpoint inhibitors. In this review, we summarize immune dysfunction in patients with MM, and review the preclinical and clinical data regarding checkpoint inhibitors in myeloma. We conclude by proposing strategies to improve the efficacy and safety of checkpoint inhibitors in this population.

Full Text

Duke Authors

Cited Authors

  • Paul, B; Kang, S; Zheng, Z; Kang, Y

Published Date

  • December 2018

Published In

Volume / Issue

  • 334 /

Start / End Page

  • 87 - 98

PubMed ID

  • 30342750

Pubmed Central ID

  • PMC6309858

Electronic International Standard Serial Number (EISSN)

  • 1090-2163

Digital Object Identifier (DOI)

  • 10.1016/j.cellimm.2018.10.003


  • eng

Conference Location

  • Netherlands