在多发性骨髓瘤 (MM) 中，免疫调节药物来那度胺的早期使用导致早期治疗中来那度胺难治性 MM 患者数量增加，但其结果尚不明确。在这里，我们报告了暴露于蛋白酶体抑制剂、来那度胺难治性多发性骨髓瘤患者的治疗模式、生存结果、预后变量和流失率，这些患者接受了 1-3 种既往治疗 (LOT)。 2016 年 1 月至 2022 年 4 月期间，Flatiron Health 数据库中共有 12,767 名 MM 患者，其中 1,455 名患者符合纳入标准。最常见的后续治疗是三联疗法（41.6% 的患者）；达雷木单抗/泊马度胺/地塞米松是最常见的治疗方案 (13.2%)。真实世界中位无进展生存期 (RW-PFS) 和总生存期 (OS) 分别为 6.5 个月和 44.4 个月。既往接受过 1、2 或 3 次 LOT 的患者的 RW-PFS 相似。国际分期系统 III 期、东部肿瘤合作组表现状态 1、血红蛋白 <12 g/dL、高风险细胞遗传学以及基线时抗 CD38 抗体无效与较差的 RW-PFS 和 OS 相关。接受国家综合癌症网络首选治疗的患者和 2020 年之后接受治疗的患者的结果仍然相似。在 561 名之前接受过 1 次 LOT 治疗的患者中，LOT 2-5 的累积流失率为 85%，其中包括 25% 的患者60% 的人在没有进一步治疗的情况下死亡。既往接受过 1-3 次 LOT 治疗的来那度胺难治性 MM 患者预后较差，并且通过现有疗法病情进展迅速，这凸显了在病程早期、在患者因自然减员而死亡之前需要更有效的治疗。版权所有 © 2024血液学。

In multiple myeloma (MM), early use of the immunomodulatory drug lenalidomide has led to an increased population of patients with lenalidomide-refractory MM in early-line settings, but their outcomes are not well characterized. Here, we report treatment patterns, survival outcomes, prognostic variables, and attrition rates for patients with proteasome inhibitor-exposed, lenalidomide-refractory MM, treated with 1-3 prior lines of therapy (LOT). From 12 767 patients with MM in the Flatiron Health database between January 2016 and April 2022, 1455 met the inclusion criteria. The most common subsequent treatments were triplet combinations (41.6% of patients); daratumumab/pomalidomide/dexamethasone was the most common treatment regimen (13.2%). Median real-world progression-free survival (RW-PFS) and overall survival (OS) were 6.5 months and 44.4 months, respectively. RW-PFS was similar in patients with 1, 2, or 3 prior LOT. International Staging System stage III, Eastern Cooperative Oncology Group performance status of 1, hemoglobin <12 g/dL, high-risk cytogenetics, and refractoriness to anti-CD38 antibody at baseline were associated with worse RW-PFS and OS. Outcomes remained similar for patients who received National Comprehensive Cancer Network-preferred treatments and those who received treatments after 2020. In 561 patients with 1 prior LOT at inclusion, cumulative attrition rate from LOT 2-5 was 85%, which included 25% patients who died and 60% with no further treatment. Patients with lenalidomide-refractory MM who have received 1-3 prior LOT have poor outcomes and progress rapidly through available therapies, highlighting the need for more effective treatments early in the disease course, before patients are lost to attrition.Copyright © 2024 American Society of Hematology.