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Published on: May 15, 2019
Evaluation of the Prognostic Significance of Cereblon Protein Expression in Multiple Myeloma
Background:
Considerable progress has been made in the treatment of multiple myeloma (MM) patients with the development of various new agents that increased survival rates over the past fifteen years. Cereblon (CRBN) plays an important role in mediating the antitumor effects of immunomodulatory drugs (IMiDs) among these new agents. The aim of our study is to investigate immunohistochemically (IHC) cereblon protein expression status in MM.
Methods:
Immunohistochemically, CRBN expression and its relationship with various prognostic factors were evaluated in bone marrow biopsies of 96 patients with MM in a single centre.
Results:
Cytoplasmic and nuclear CRBN expression was detected in all neoplastic cells. While a complete or partial response to treatment was obtained in 45 patients, the disease was stable in 13 and progressive in 17 patients. Survival was longer in those treated with IMiD-containing regimens (p = 0.044). Both the survival rate (p = 0.013) and the survival time were significantly increased (p = 0.023) in those who received the treatment protocol containing protease inhibitors. A significant relationship was found between the treatment protocol and treatment response in the chi-squared analysis (p = 0.008). Although the longest survival time - though not statistically significant - was detected in the group treated with protease inhibitors (log rank, p = 0.217). The survival analysis revealed the presence of a relationship between IgG and IgA positivity and survival.
Conclusions:
In this study, the survival time of the patients who received treatment regimens containing protease inhibitors and IMiD was longer, independent of the presence of strong nuclear CRBN expression. The survival rate was significantly higher in those who used IMiD and protease inhibitors in combination. Since the survival rate was found to be increased in IgG positive cases and we thought that evaluation of immunoglobulin tissue expression in MM cases can provide prognostic prediction.
Insights
Immunomodulatory drugs (IMiDs) and protease inhibitors improve survival in multiple myeloma (MM) patients. Cereblon (CRBN) expression did not impact survival, but combinations of IMiDs and protease inhibitors significantly increased survival rates.
Area of Science:
- Hematology
- Oncology
- Immunology
Background:
- Multiple myeloma (MM) treatment has advanced, improving patient survival.
- Cereblon (CRBN) is crucial for the efficacy of immunomodulatory drugs (IMiDs).
- Investigating CRBN expression in MM is important for understanding treatment response.
Purpose of the Study:
- To evaluate immunohistochemical (IHC) cereblon (CRBN) protein expression in multiple myeloma (MM) patients.
- To correlate CRBN expression with prognostic factors and treatment outcomes.
Main Methods:
- Bone marrow biopsies from 96 MM patients were analyzed using immunohistochemistry (IHC).
- CRBN expression was assessed in relation to treatment protocols and patient survival.
- Statistical analyses, including chi-squared and log-rank tests, were employed.
Main Results:
- Cytoplasmic and nuclear CRBN expression was universally detected in MM cells.
- Patients receiving IMiD-containing regimens showed longer survival (p=0.044).
- Treatment with protease inhibitors significantly increased survival rate (p=0.013) and time (p=0.023).
- A significant association was found between treatment protocols and response (p=0.008).
- IgG and IgA positivity correlated with improved survival.
Conclusions:
- Treatment regimens combining protease inhibitors and IMiDs led to longer survival in MM patients.
- Survival benefits were observed irrespective of strong nuclear CRBN expression.
- Combined IMiD and protease inhibitor therapy significantly enhanced survival rates.
- Immunoglobulin (IgG, IgA) tissue expression may offer prognostic value in MM.
