Long-term proteasome inhibitor (PI) treatment can improve multiple myeloma (MM) outcomes, but this can be difficult to achieve in clinical practice due to toxicity, comorbidities, and the burden of repeated parenteral administration. US MM-6 (NCT03173092) enrolled transplant-ineligible patients with newly diagnosed MM to receive all-oral ixazomib-lenalidomide-dexamethasone (IRd; ≤39 cycles or until progression or toxicity) following three cycles of bortezomib-based induction. Primary endpoint: 2-year progression-free survival (PFS). Key secondary/exploratory endpoints included overall response rate (ORR), overall survival (OS), safety, quality of life (QoL), treatment satisfaction, and actigraphy. At datacut, in the fully accrued cohort of 140 patients, median age was 73 years with 42% aged ≥75 and 61% deemed frail; 10% of patients were ongoing on treatment. After a median follow-up of 27 months, the 2-year PFS rate was 71% (95% confidence interval: 61–78). ORR increased from 62% at the end of induction to 80% following in-class transition (iCT) to IRd for a median of 11 months. The 2-year OS rate was 86%. The overall safety profile/actigraphy levels were consistent with previous reports; QoL/treatment satisfaction scores were stable with ongoing therapy. iCT to IRd may allow prolonged PI-based therapy with promising efficacy and a tolerable safety profile, while maintaining QoL.
长期使用蛋白酶体抑制剂（PI）治疗可改善多发性骨髓瘤（MM）的预后，但由于毒性、合并症及重复肠外给药负担，在临床实践中往往难以实现。美国MM-6研究（NCT03173092）入组了不适合移植的新诊断MM患者，在完成三个周期基于硼替佐米的诱导治疗后，接受全口服方案伊沙佐米-来那度胺-地塞米松（IRd；≤39个周期或直至疾病进展或出现毒性）治疗。主要终点为2年无进展生存期（PFS）。关键次要/探索性终点包括总缓解率（ORR）、总生存期（OS）、安全性、生活质量（QoL）、治疗满意度和体动记录监测。截至数据截点，在完整入组的140例患者队列中，中位年龄73岁，其中42%年龄≥75岁，61%为虚弱患者；10%的患者仍在继续治疗。中位随访27个月后，2年PFS率为71%（95%置信区间：61–78）。ORR从诱导治疗结束时的62%提升至同类转换（iCT）至IRd治疗中位11个月后的80%。2年OS率为86%。总体安全性特征/体动记录水平与既往报告一致；生活质量/治疗满意度评分在持续治疗期间保持稳定。转换至IRd治疗可能实现基于PI的长期治疗，具有良好疗效和可耐受的安全性，同时维持生活质量。
肿瘤(癌症)患者之家