Monitoring bortezomib therapy in multiple myeloma: screening of cyclin D1, D2, and D3 via reliable real-time polymerase chain reaction and association with clinico-pathological features and outcome

Abstract

Cyclins D1, D2, and D3 (CCND1, 2, 3) are regulated by proteasomal degradation. Their overexpression in multiple myeloma (MM) has prognostic value. We performed this pilot study to analyze a possible association between CCND1–3 overexpression and response to treatment with the proteasome inhibitor bortezomib, since a specific prognostic marker for bortezomib response has not been reported, but would be ideal to predict who benefits most from bortezomib in times of several potentially efficient therapeutic options. Bone marrow (BM) specimens of 20/47 consecutive patients were available for reliable CCND1–3 analyses by real-time PCR. With CCND1 overexpression in 9/20 patients, the risk for progression after bortezomib treatment was significantly decreased (HR 0.102, 95% CI 0.021–0.498, p = 0.0048) and progression-free survival substantially prolonged (p = 0.0011). Our study is the first to suggest that overexpressed CCND1 in MM is an independent prognostic marker associated with a more durable response to bortezomib. These preliminary results warrant a larger study.

Keywords:

• Bortezomib
• cell cycle
• cyclin D1
• multiple myeloma
• proteasome
• ubiquitin

Acknowledgements

We are grateful to Prof. R. Mertelsmann for his ongoing support and Mrs. Carole Cürten for proof-reading.

Declaration of interest: This work was supported in part by the Deutsche Krebshilfe (R.W.) and Biotera Foundation (M.E.).