The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies.
The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies.
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DOI：
10.1186/s40364-021-00344-2
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发表时间：
2022-01-09
影响因子：
11.1
通讯作者：
Lahuerta JJ
中科院分区：
文献类型：
--
作者：
Hernández-Rivas JÁ;Ríos-Tamayo R;Encinas C;Alonso R;Lahuerta JJ
新诊断和复发/难治性多发性骨髓瘤（RRMM）患者的治疗替代方案数量的增加扩大了临床情况，导致迄今为止没有算法能够覆盖的复杂性水平。目前，由于MM患者在达到复发性/难治性疾病状态之前发现的各种临床情况，这种复杂性有所增加。这些不同的背景可能包括原发性难治性，完成最新一代药物一线治疗后的早期复发，或化疗或自体移植后的极晚期复发。同样重要的是要记住，许多患者的资料在主要的随机临床试验（RCT）中没有得到充分的代表，这进一步使治疗决策复杂化。在RRMM患者中，既往未使用药物的选择以及既往治疗方案的数量和持续时间直至进展对治疗疗效的影响大于MM本身的不良生物学特征。除了蛋白酶体抑制剂、免疫调节药物、抗CD 38抗体和皮质类固醇外，还开发了新一代药物，如XPO抑制剂、BCL-2抑制剂、新型烷化剂，最重要的是，基于结合抗BCMA抗体和CAR-T细胞的免疫疗法，以对抗RRMM。这一全面的审查解决的基本面和有关RRMM的争议，并讨论了管理和治疗的主要方面。RRMM临床管理的基础（临床情况的复杂性，选择适当治疗或何时治疗前要考虑的关键因素），与既往标准一线治疗方案无交叉耐药性的新药库（主要3期临床试验），未来前景，包括废弃资源的有用性，连同围绕RRMM患者的临床管理的争议将详细审查。
The increase in the number of therapeutic alternatives for both newly diagnosed and relapsed/refractory multiple myeloma (RRMM) patients has widened the clinical scenario, leading to a level of complexity that no algorithm has been able to cover up to date. At present, this complexity increases due to the wide variety of clinical situations found in MM patients before they reach the status of relapsed/refractory disease. These different backgrounds may include primary refractoriness, early relapse after completion of first-line therapy with latest-generation agents, or very late relapse after chemotherapy or autologous transplantation. It is also important to bear in mind that many patient profiles are not fully represented in the main randomized clinical trials (RCT), and this further complicates treatment decision-making. In RRMM patients, the choice of previously unused drugs and the number and duration of previous therapeutic regimens until progression has a greater impact on treatment efficacy than the adverse biological characteristics of MM itself. In addition to proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies and corticosteroids, a new generation of drugs such as XPO inhibitors, BCL-2 inhibitors, new alkylators and, above all, immunotherapy based on conjugated anti-BCMA antibodies and CAR-T cells, have been developed to fight RRMM. This comprehensive review addresses the fundamentals and controversies regarding RRMM, and discusses the main aspects of management and treatment. The basis for the clinical management of RRMM (complexity of clinical scenarios, key factors to consider before choosing an appropriate treatment, or when to treat), the arsenal of new drugs with no cross resistance with previously administered standard first line regimens (main phase 3 clinical trials), the future outlook including the usefulness of abandoned resources, together with the controversies surrounding the clinical management of RRMM patients will be reviewed in detail.
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