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)

Abstract

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
• biomarkers
• IMiDs
• multiple myeloma

Acknowledgements

The authors want to thank Julia Heppke, Iris Oberauer, and Claudia Zavadil for excellent technical assistance. This work was supported by the European Union Seventh Framework Programme (FP7/2007–2013) OPTATIO [n°278570], as well as by the COMET Center ONCOTYROL.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.3109/10428194.2016.1144880