Purpose of Review

The development of potent novel agents has improved outcomes for patients with multiple myeloma (MM). Heterogeneity of response to therapy, an expanding arsenal of treatment options, and cost are however major challenges for physicians making treatment decisions. Response-adapted therapy is hence an attractive strategy for sequencing of therapy in MM. Despite its successful application in other haematologic malignancies, response-adapted therapy is yet to become a standard of care for MM. We provide our perspective on response-adapted therapeutic strategies evaluated thus far and how they may be implemented and improved on in treatment algorithms of the future.

Recent Findings

While older studies suggested that early response based on International Myeloma Working Group response criteria could impact long-term outcomes, recent data have contradicted these findings. The advent of minimal residual disease (MRD) as a powerful prognostic factor in MM has raised the promise of MRD-adapted treatment strategies. The development of more sensitive techniques for paraprotein quantification as well as imaging modalities to detect extramedullary disease is likely to change response assessment in MM. These techniques combined with MRD assessment may provide sensitive and holistic response assessments which could be evaluated in clinical trials.

Summary

Response-adapted treatment algorithms have the potential to allow an individualised treatment strategy, maximising efficacy, while minimising toxicities and cost. Standardisation of MRD methodology, incorporation of imaging into response assessment, and the optimal management of MRD positive patients are key questions to be addressed in future trials.

中文翻译：

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新诊断的多发性骨髓瘤的反应适应疗法

审查目的

强效新药的开发改善了多发性骨髓瘤 (MM) 患者的预后。然而，治疗反应的异质性、治疗选择的不断扩大以及成本是医生做出治疗决策的主要挑战。因此，适应反应的治疗对于 MM 的治疗顺序来说是一种有吸引力的策略。尽管反应适应疗法已成功应用于其他血液系统恶性肿瘤，但它尚未成为 MM 的护理标准。我们提供了对迄今为止评估的适应反应的治疗策略的看法，以及如何在未来的治疗算法中实施和改进它们。

最近的发现

虽然较早的研究表明，基于国际骨髓瘤工作组应对标准的早期应对可能会影响长期结果，但最近的数据与这些发现相矛盾。微小残留病 (MRD) 作为 MM 强有力的预后因素的出现，提高了适应 MRD 的治疗策略的前景。开发更灵敏的副蛋白定量技术以及检测髓外疾病的成像方式可能会改变 MM 的反应评估。这些技术与 MRD 评估相结合可以提供敏感和整体的反应评估，可以在临床试验中进行评估。

概括

适应反应的治疗算法有可能实现个体化治疗策略，最大限度地提高疗效，同时最大限度地降低毒性和成本。MRD 方法的标准化、将影像学纳入疗效评估以及 MRD 阳性患者的最佳管理是未来试验中需要解决的关键问题。