Survival of multiple myeloma (MM) has significantly improved over the past decade; however, a composed group of patients (15% to 20%), named high-risk (HR) MM, still experiences reduced survival. Both tumor biology and suboptimal/absent responses to therapy may underlie HR definition and a clear uniform identification of risk factors is crucial for proper management of these patients. In biologic HRMM, MRD attaining and sustaining negativity, inside and outside bone marrow, should be the primary goal and therapy should be adapted in patients with frailty to reduce toxicity and improve quality of life. MM treatment has traditionally been tailored to age and more recently frailty or comorbidities, but very rarely to the biology of the disease, mainly because of the lack of a clear benefit derived from a specific drug/combination, inhomogeneity in HR definition, and lack of data coming from prospective, properly designed clinical trials. Some attempts have been successfully made in this direction. In this review, we discuss the current definitions of HR and the need for a consensus, the results of available trials in HR patients, and the way through risk-adapted treatment strategies. For this purpose, we propose several clinical cases of difficult-to-treat patients throughout different treatment phases.

中文翻译：

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我如何治疗高危多发性骨髓瘤。

在过去十年中，多发性骨髓瘤 (MM) 的存活率显着提高；然而，一组名为高危 (HR) MM 的患者（15% 至 20%）仍然存在生存率降低的情况。肿瘤生物学和对治疗的次优/无反应可能是 HR 定义的基础，明确统一识别风险因素对于正确管理这些患者至关重要。在生物 HRMM 中，骨髓内外的 MRD 达到和维持阴性应该是主要目标，并且应对虚弱患者调整治疗以减少毒性和提高生活质量。MM 治疗传统上是针对年龄和最近的虚弱或合并症量身定制的，但很少针对疾病的生物学，主要是因为缺乏从特定药物/组合中获得的明显益处，人力资源定义的不均匀性，以及缺乏来自前瞻性、设计合理的临床试验的数据。在这个方向上已经成功地进行了一些尝试。在这篇综述中，我们讨论了 HR 的当前定义和达成共识的必要性、HR 患者可用试验的结果，以及通过风险适应治疗策略的方式。为此，我们提出了几个不同治疗阶段的难治患者的临床病例。