A wide variety of new therapeutic options for Multiple Myeloma (MM) have recently become available, extending progression-free and overall survival for patients in meaningful ways. However, these treatments are not curative, and patients eventually relapse, necessitating decisions on the appropriate choice of treatment(s) for the next phase of the disease. Additionally, an important subset of MM patients will prove to be refractory to the majority of the available treatments, requiring selection of effective therapies from the remaining options. Immunomodulatory agents (IMiDs), proteasome inhibitors, monoclonal antibodies, and alkylating agents are the major classes of MM therapies, with several options in each class. Patients who are refractory to one agent in a class may be responsive to a related compound or to a drug from a different class. However, rules for selection of alternative treatments in these situations are somewhat empirical and later phase clinical trials to inform those choices are ongoing. To address these issues the NCI Multiple Myeloma Steering Committee formed a relapsed/refractory working group to review optimal treatment choices, timing, and sequencing and provide recommendations. Additional issues considered include the role of salvage autologous stem cell transplantation, risk stratification, targeted approaches for genetic subsets of MM, appropriate clinical trial endpoints, and promising investigational agents. This report summarizes the deliberations of the working group and suggests potential avenues of research to improve the precision, timing, and durability of treatments for Myeloma.

最近出现了多种针对多发性骨髓瘤 (MM) 的新治疗方案，以有意义的方式延长了患者的无进展生存期和总生存期。然而，这些治疗方法并不能治愈，患者最终会复发，因此需要为疾病的下一阶段选择适当的治疗方法。此外，MM 患者的一个重要子集将被证明对大多数可用的治疗方法无效，需要从剩余的治疗方案中选择有效的治疗方法。免疫调节剂 (IMiD)、蛋白酶体抑制剂、单克隆抗体和烷化剂是 MM 治疗的主要类别，每一类都有多种选择。对一类药物耐药的患者可能对相关化合物或不同类别的药物有反应。然而，在这些情况下选择替代治疗的规则在某种程度上是经验性的，并且正在进行后期临床试验以告知这些选择。为了解决这些问题，NCI 多发性骨髓瘤指导委员会成立了一个复发/难治性工作组，以审查最佳治疗选择、时机和测序并提供建议。考虑的其他问题包括挽救性自体干细胞移植的作用、风险分层、针对 MM 遗传亚型的针对性方法、适当的临床试验终点和有前途的研究药物。本报告总结了工作组的审议结果，并提出了提高骨髓瘤治疗的精确度、时机和持久性的潜在研究途径。