Bila Jelena, Sretenovic Aleksandra, Jelicic Jelena, Tosic Natasa, Glumac Irena, Fekete Marija Dencic, Antic Darko, Balint Milena Todorovic, Markovic Olivera, Milojevic Zoran, Radojkovic Milica, Trajkovic Goran, Puric Mila, Pavlovic Sonja, Mihaljevic Biljana
Multiple Myeloma Unit of Lymphoma Center, Clinic of Haematology, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Multiple Myeloma Unit of Lymphoma Center, Clinic of Haematology, Clinical Center of Serbia, Belgrade, Serbia.
Clin Lymphoma Myeloma Leuk. 2016 Nov;16(11):610-615. doi: 10.1016/j.clml.2016.08.007. Epub 2016 Aug 10.
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.
为了使多发性骨髓瘤（MM）患者的治疗方法个性化，诸如脑啡肽酶（CRBN）等分子标志物目前是研究的重点。本研究的目的是检验CRBN表达在不适合自体干细胞移植（ASCT）的MM患者中的预后意义。
分析了92例既往未接受治疗的患者的数据。根据国际分期系统评分，1分、2分和3分的患者分布分别为26.1%、30.4%和43.5%。分别有83.7%和16.3%的患者使用了基于沙利度胺和硼替佐米的联合方案。
83.7%的患者获得了治疗反应（完全缓解、非常好的部分缓解、部分缓解），且与高CRBN表达相关（P = .006），主要见于接受沙利度胺治疗的患者（P = .028）。低CRBN表达影响接受沙利度胺治疗患者的无进展生存期（PFS；P = .017），但不影响总生存期（OS），在硼替佐米组中对OS无影响。在Cox回归模型中，低CRBN表达是影响接受沙利度胺治疗患者PFS的最重要预后参数（P = .012）。
对于不适合ASCT且接受沙利度胺作为免疫调节药物治疗的MM患者，CRBN表达具有预后价值。低表达表明可能治疗效果欠佳，检测CRBN表达可能作为个性化治疗方法中的额外预后工具。
