The Role of CELMoD Agents in Multiple Myeloma.

IF 2.8 4区 医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
OncoTargets and therapy Pub Date : 2025-08-27 eCollection Date: 2025-01-01 DOI:10.2147/OTT.S398118
Niels W C J van de Donk, Nizar J Bahlis, Charlotte Pawlyn, Francesca Gay, Maria-Victoria Mateos, Katja Weisel, Sagar Lonial, Paul G Richardson
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引用次数: 0

Abstract

Although recent decades have seen continued improvements in survival for patients with multiple myeloma, the disease remains largely incurable, and most patients will experience relapse and/or become refractory to treatment. There thus remains an urgent unmet need for novel treatments, particularly for those patients with relapsed or refractory multiple myeloma. Novel treatment modalities, such as targeted protein degradation, have attracted particular interest due to their ability to expand the range of druggable protein targets in myeloma cells. Iberdomide (CC-220) and mezigdomide (CC-92480) are promising oral CELMoD™ agents currently being evaluated for the treatment of patients with multiple myeloma. Preclinical data from lenalidomide- and pomalidomide-resistant cell lines and mouse models suggest that iberdomide and mezigdomide have the potential to provide therapeutic benefit even in patients who are refractory to lenalidomide and pomalidomide. The optimized specificity, potency, and safety profile of iberdomide and mezigdomide supports their clinical use and aligns with the need for longer durations of a well-tolerated oral CELMoD agent with synergistic combinability with other immune approaches (such as anti-CD38 monoclonal antibodies) and proteasome inhibitors (such as bortezomib and carfilzomib). Although neither iberdomide or mezigdomide has yet received regulatory approval for the treatment of multiple myeloma, based on their mechanism of action and the data available to date, we propose that both drugs may be attractive options for the treatment of patients with relapsed or refractory multiple myeloma; based on their efficacy and safety profiles, iberdomide is likely better suited for use in newly diagnosed, first relapse, or maintenance settings, whereas mezigdomide may also be better suited for use in patients with early relapse or a greater number of prior antimyeloma treatments. Iberdomide and mezigdomide are currently being evaluated for the treatment of patients with multiple myeloma in several trials, and results so far are promising.

Abstract Image

CELMoD制剂在多发性骨髓瘤中的作用。
尽管近几十年来多发性骨髓瘤患者的生存率不断提高,但这种疾病在很大程度上仍然无法治愈,大多数患者会复发和/或难以治疗。因此,迫切需要新的治疗方法,特别是那些复发或难治性多发性骨髓瘤患者。新的治疗方式,如靶向蛋白质降解,由于它们能够扩大骨髓瘤细胞中可药物蛋白靶点的范围而引起了特别的兴趣。Iberdomide (CC-220)和mezigdomide (CC-92480)是有前景的口服CELMoD™药物,目前正在评估用于治疗多发性骨髓瘤患者。来那度胺和波马度胺耐药细胞系和小鼠模型的临床前数据表明,伊伯多胺和美西多胺即使对来那度胺和波马度胺难治的患者也有可能提供治疗益处。优化后的伊伯多胺和美西多胺的特异性、效力和安全性支持了它们的临床应用,并符合耐受性良好的口服CELMoD药物与其他免疫方法(如抗cd38单克隆抗体)和蛋白酶体抑制剂(如硼替佐米和卡非佐米)协同联合使用更长时间的需求。尽管伊伯多胺或美西多胺尚未获得监管部门批准用于多发性骨髓瘤的治疗,但基于其作用机制和迄今为止可用的数据,我们认为这两种药物可能是治疗复发或难治性多发性骨髓瘤患者的有吸引力的选择;基于其有效性和安全性,伊伯多胺可能更适合用于新诊断、首次复发或维持环境,而美西多胺也可能更适合用于早期复发或先前接受过大量抗骨髓瘤治疗的患者。Iberdomide和mezigdomide目前正在几项试验中对多发性骨髓瘤患者的治疗进行评估,到目前为止结果很有希望。
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来源期刊
OncoTargets and therapy
OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY
CiteScore
9.70
自引率
0.00%
发文量
221
审稿时长
1 months
期刊介绍: OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.
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