Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Hematology, Cancer Center Amsterdam, Amsterdam, Netherlands.
The Institute of Cancer Research, The Royal Marsden Hospital NHS Foundation Trust, London, UK.
Lancet. 2021 Jan 30;397(10272):410-427. doi: 10.1016/S0140-6736(21)00135-5.
Multiple myeloma is the second most common haematological malignancy in high-income countries, and typically starts as asymptomatic precursor conditions-either monoclonal gammopathy of undetermined significance or smouldering multiple myeloma-in which initiating genetic abnormalities, such as hyperdiploidy and translocations involving the immunoglobulin heavy chain, are already present. The introduction of immunomodulatory drugs, proteasome inhibitors, and CD38-targeting antibodies has extended survival, but ultimately the majority of patients will die from their disease, and some from treatment-related complications. Disease progression and subsequent relapses are characterised by subclonal evolution and increasingly resistant disease. Patients with multiple myeloma usually have hypercalcaemia, renal failure, anaemia, or osteolytic bone lesions-and a detailed diagnostic investigation is needed to differentiate between symptomatic multiple myeloma that requires treatment, and precursor states. Risk stratification using both patient-specific (eg, performance status) and disease-specific (eg, presence of high-risk cytogenetic abnormalities) is important for prognosis and to define the best treatment strategy. Current research strategies include the use of minimal residual disease assays to guide therapy, refining immunotherapeutic approaches, and intercepting disease early in smouldering multiple myeloma.
多发性骨髓瘤是高收入国家中第二常见的血液系统恶性肿瘤，通常起始于无症状的前驱状态——单克隆丙种球蛋白病（意义未明）或冒烟型多发性骨髓瘤，此时已经存在起始遗传异常，如超二倍体和涉及免疫球蛋白重链的易位。免疫调节剂、蛋白酶体抑制剂和 CD38 靶向抗体的应用延长了患者的生存时间，但大多数患者最终仍会死于疾病，部分患者则死于治疗相关并发症。疾病进展和随后的复发表现为亚克隆进化和疾病耐药性增加。多发性骨髓瘤患者通常有高钙血症、肾衰竭、贫血或溶骨性骨病变，需要进行详细的诊断性检查来区分需要治疗的症状性多发性骨髓瘤和前驱状态。使用患者特异性（如一般状态）和疾病特异性（如存在高危细胞遗传学异常）的风险分层对预后和确定最佳治疗策略很重要。目前的研究策略包括使用微小残留病检测来指导治疗、改进免疫治疗方法以及在冒烟型多发性骨髓瘤早期截获疾病。
