Lee Byung-Hyun, Kang Ka-Won, Jeon Min Ji, Yu Eun Sang, Kim Dae Sik, Lee Se Ryeon, Sung Hwa Jung, Park Yong, Choi Chul Won, Kim Byung Soo
Department of Internal Medicine, Korea University College of Medicine, Anam Hospital, Seoul, South Korea.
Department of Internal Medicine, Korea University College of Medicine, Guro Hospital, Seoul, South Korea.
Front Oncol. 2021 Jul 14;11:687361. doi: 10.3389/fonc.2021.687361. eCollection 2021.
Cereblon (CRBN) is a direct target of immunomodulatory drugs (IMiDs) and is known to be sensitive and responsive to IMiD therapy. We evaluated CRBN expression in bone marrow plasma cells and analyzed whether CRBN expression was associated with multiple myeloma prognosis. Lastly, we developed a nomogram model for predicting high CRBN expression based on clinically significant blood markers.
We evaluated 143 multiple myeloma patients (internal dataset) who underwent bone marrow examinations. For evaluating the prognostic ability of the nomogram model, two external cohorts (235 patients in external dataset 1 and 156 patients in external dataset 2) were analyzed. The expression of CRBN in bone marrow aspirate samples was evaluated using immunohistochemistry. High CRBN expression was defined as the study-defined H-score ≥6.
In the high CRBN group, the median progression-free survival (PFS) and overall survival (OS) of patients receiving the IMiD-based therapy and non-IMiD therapy were 29 and 10 months for PFS, and NR (not reached) and 54 months for OS, respectively. IMiD-based therapy was significantly associated with better PFS and OS outcomes. High CRBN expression was independently predicted by female sex, high serum free-light chain (FLC) ratio, higher serum M-protein level, and higher β2-microglobulin level. Based on these results, we constructed a new nomogram model to predict high CRBN expression and the effectiveness of IMiD therapy in multiple myeloma.
This nomogram could improve the prognostic evaluation of myeloma patients exhibiting high CRBN expression treated with IMiD therapy and might help provide personalized treatment strategies to clinicians.
Cereblon（CRBN）是免疫调节药物（IMiDs）的直接靶点，已知对IMiD治疗敏感且有反应。我们评估了骨髓浆细胞中CRBN的表达，并分析了CRBN表达是否与多发性骨髓瘤的预后相关。最后，我们基于具有临床意义的血液标志物开发了一种预测高CRBN表达的列线图模型。
我们评估了143例接受骨髓检查的多发性骨髓瘤患者（内部数据集）。为了评估列线图模型的预后能力，分析了两个外部队列（外部数据集1中的235例患者和外部数据集2中的156例患者）。使用免疫组织化学评估骨髓穿刺样本中CRBN的表达。高CRBN表达定义为研究定义的H评分≥6。
在高CRBN组中，接受基于IMiD的治疗和非IMiD治疗的患者的无进展生存期（PFS）和总生存期（OS）的中位数，PFS分别为29个月和10个月，OS分别为未达到（NR）和54个月。基于IMiD的治疗与更好的PFS和OS结果显著相关。女性、高血清游离轻链（FLC）比值、更高的血清M蛋白水平和更高的β2微球蛋白水平可独立预测高CRBN表达。基于这些结果，我们构建了一个新的列线图模型，以预测多发性骨髓瘤中高CRBN表达和IMiD治疗的有效性。
该列线图可以改善接受IMiD治疗的高CRBN表达骨髓瘤患者的预后评估，并可能有助于为临床医生提供个性化的治疗策略。
