Low Beclin-1 expression predicts improved overall survival in patients treated with immunomodulatory drugs for multiple myeloma and identifies autophagy inhibition as a promising potentially druggable new therapeutic target: an analysis from The Austrian Myeloma Registry (AMR)

Leuk Lymphoma. 2016 Oct;57(10):2330-41. doi: 10.3109/10428194.2016.1144880. Epub 2016 Feb 16.


Beclin-1 is a key regulator of autophagy and has been suggested to be involved in the development of drug resistance in multiple myeloma (MM). We analyzed the expression of Beclin-1 in a retrospective cohort of 70 MMs. Beclin-1 expression did not influence overall survival (OS) and progression-free survival (PFS) in patients with therapy-naïve MM. In patients treated with immunomodulatory drugs (IMiDs) lack of or low Beclin-1 expression resulted in a significantly improved OS and PFS compared to those treated with bortezomib or nonnovel agents. Beclin-1 expression was more frequently detected in relapsed MM than in therapy-naïve MM probably being a hallmark of tumor progression and therapy resistance. If validated prospectively, Beclin-1 expression might identify patients prone to profit above average from IMiDs and enable a more rational allocation of antimyeloma therapies. Furthermore, the inhibition of autophagy could be a new promising target to improve response to treatment in the relapsed/refractory setting.

Keywords: Autophagy; Beclin-1; IMiDs; biomarkers; multiple myeloma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols
  • Autophagy / drug effects
  • Beclin-1 / genetics*
  • Beclin-1 / metabolism
  • Biomarkers
  • Disease Progression
  • Drug Synergism
  • Female
  • Gene Expression*
  • Humans
  • Immunohistochemistry
  • Immunologic Factors / pharmacology*
  • Immunologic Factors / therapeutic use
  • Male
  • Middle Aged
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / mortality*
  • Neoplasm Staging
  • Survival Analysis
  • Treatment Outcome


  • Antineoplastic Agents
  • Beclin-1
  • Biomarkers
  • Immunologic Factors