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.
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.
Ngo
Ba Thanh-Truc
BT
Department of Hematology and Oncology, University Medical Center, Freiburg, Germany.
Felthaus
Julia
J
Hein
Manuel
M
Follo
Marie
M
Wider
Dagmar
D
Ihorst
Gabriele
G
Engelhardt
Monika
M
Wäsch
Ralph
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001853:Bone Marrow; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D056742:Cyclin D2 / Q000235:genetics* / Q000378:metabolism; D056743:Cyclin D3 / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000032:analysis / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D011719:Pyrazines / Q000627:therapeutic use*; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001897:Boronic Acids; C530104:CCND1 protein, human; C080336:CCND2 protein, human; C534696:CCND3 protein, human; D056742:Cyclin D2; D056743:Cyclin D3; D011719:Pyrazines; D019938:Cyclin D1; D000069286:Bortezomib; D004247:DNA