Resistance to Proteasome Inhibitors and other Targeted Therapies in Myeloma

Craig Wallington-Beddoe, Magdalena Sobieraj-Teague, Bryone Kuss, Stuart Pitson

Research output: Contribution to journalReview articlepeer-review

45 Citations (Scopus)


The number of novel therapies for the treatment of myeloma is rapidly increasing, as are the clinical trials evaluating them in combination with other novel and established therapies. Proteasome inhibitors, immunomodulatory agents and monoclonal antibodies are the most well known and studied classes of novel agents targeting myeloma, with histone deacetylase inhibitors, nuclear export inhibitors and several other approaches also being actively investigated. However, in parallel with the development and clinical use of these novel myeloma therapies is the emergence of novel mechanisms of resistance, many of which remain elusive, particularly for more recently developed agents. Whilst resistance mechanisms have been best studied for proteasome inhibitors, particularly bortezomib, class effects do not universally apply to all class members, and within-class differences in efficacy, toxicity and resistance mechanisms have been observed. Although immunomodulatory agents share the common cellular target cereblon and thus resistance patterns relate to cereblon expression, the unique cell surface antigens to which monoclonal antibodies are directed means these agents frequently exhibit unique within-class differences in clinical efficacy and resistance patterns. This review describes the major classes of novel therapies for myeloma, highlights the major clinical trials within each class and discusses known resistance mechanisms.

Original languageEnglish
Pages (from-to)11-28
Number of pages18
JournalBritish Journal of Haematology
Issue number1
Publication statusPublished - Jul 2018


  • immunomodulatory agent
  • monoclonal antibody
  • myeloma
  • novel therapy
  • proteasome inhibitor
  • resistance mechanisms


Dive into the research topics of 'Resistance to Proteasome Inhibitors and other Targeted Therapies in Myeloma'. Together they form a unique fingerprint.

Cite this