Prognostic Significance of Cereblon Expression in Patients With Multiple Myeloma.
To personalize the treatment approach for patients with multiple myeloma (MM), molecular markers such as cereblon (CRBN) are currently the focus of investigation. The aim of the present study was to test the prognostic significance of CRBN expression in MM patients ineligible for autologous stem cell transplantation (ASCT).



The data from 92 previously untreated patients were analyzed. The distribution according to the International Staging System score was 26.1%, 30.4%, and 43.5% with a score of 1, 2, and 3, respectively. Thalidomide- and bortezomib-based combinations were used in 83.7% and 16.3% of the patients, respectively.



A treatment response (complete remission, very good partial remission, partial remission) was achieved in 83.7% of the patients and correlated with high CRBN expression (P = .006), mainly in the patients treated with thalidomide (P = .028). Low CRBN expression affected progression-free survival (PFS; P = .017) but not overall survival (OS) in patients treated with thalidomide and had no influence on OS in the bortezomib group. In the Cox regression model, low CRBN expression was the most important prognostic parameter that influenced PFS in the thalidomide-treated patients (P = .012).



CRBN expression is of prognostic value in MM patients ineligible for ASCT treated with thalidomide as an immunomodulatory drug. With low expression indicating a possible suboptimal treatment outcome, measurement of CRBN expression might serve as additional prognostic tool in the personalized treatment approach.
Multiple Myeloma Unit of Lymphoma Center, Clinic of Haematology, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia. Electronic address: biladr.jelena@gmail.com.
Jelena
J
Bila
Multiple Myeloma Unit of Lymphoma Center, Clinic of Haematology, Clinical Center of Serbia, Belgrade, Serbia.
Aleksandra
A
Sretenovic
Multiple Myeloma Unit of Lymphoma Center, Clinic of Haematology, Clinical Center of Serbia, Belgrade, Serbia.
Jelena
J
Jelicic
Laboratory of Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Natasa
N
Tosic
Laboratory of Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Irena
I
Glumac
Multiple Myeloma Unit of Lymphoma Center, Clinic of Haematology, Clinical Center of Serbia, Belgrade, Serbia.
Marija Dencic
MD
Fekete
Multiple Myeloma Unit of Lymphoma Center, Clinic of Haematology, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Darko
D
Antic
Multiple Myeloma Unit of Lymphoma Center, Clinic of Haematology, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Milena Todorovic
MT
Balint
Department of Haematology, Clinical Hospital Centre Bezanijska Kosa, Belgrade, Serbia.
Olivera
O
Markovic
Department of Haematology, Clinical Hospital Centre Zvezdara, Belgrade, Serbia.
Zoran
Z
Milojevic
Department of Haematology, Clinical Hospital Centre Dragisa Misovic, Belgrade, Serbia.
Milica
M
Radojkovic
Faculty of Medicine, Institute for Medical Statistics and Informatics, University of Belgrade, Belgrade, Serbia.
Goran
G
Trajkovic
Hematology Divison, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia.
Mila
M
Puric
Laboratory of Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Sonja
S
Pavlovic
Multiple Myeloma Unit of Lymphoma Center, Clinic of Haematology, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Biljana
B
Mihaljevic
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D009367:Neoplasm Staging; D010447:Peptide Hydrolases / Q000235:genetics*; D011379:Prognosis; D016896:Treatment Outcome; D044767:Ubiquitin-Protein Ligases
D048868:Adaptor Proteins, Signal Transducing; C502543:CRBN protein, human; D044767:Ubiquitin-Protein Ligases; D010447:Peptide Hydrolases
CRBN expression; Immunomodulatory drugs; Multiple myeloma; Prognosis; Treatment