Isatuximab plus bortezomib, lenalidomide, and dexamethasone for transplant-ineligible newly diagnosed multiple myeloma patients: a frailty subgroup analysis of the IMROZ trial.

Here, we present a post hoc subgroup analysis of IMROZ, a global, phase III, open-label study investigating isatuximab (Isa) with bortezomib, lenalidomide, and dexamethasone (VRd) followed by Isa-Rd (N=265) versus VRd followed by Rd (N=181) in newly diagnosed transplant-ineligible MM (Ti NDMM) patients using the simplified International Myeloma Working Group (sIMWG) frailty score.

在这里，我们展示了IMROZ的回顾性亚组分析结果，这是一项全球性的III期、开放标签研究，研究对象为新诊断的不符合移植条件的多发性骨髓瘤（Ti NDMM）患者。研究比较了使用简化国际骨髓瘤工作组（sIMWG）虚弱评分系统，对接受Isatuximab（Isa）联合硼替佐米、雷那度胺和地塞米松（VRd）后转为Isa-Rd治疗（N=265）与仅接受VRd后转为Rd治疗（N=181）的患者进行比较。

Although patients aged >80 years were excluded, there was no exclusion for patients meeting frailty criteria.

尽管排除了年龄大于80岁的患者，但对符合虚弱标准的患者没有排除。

All patients received standard VRd/Rd dosing; Isa-VRd patients received intravenous Isa (cycle 1, 10 mg/kg once weekly; cycles 2-17, once every 2 weeks; subsequent cycles, once every 4 weeks).

所有患者均接受了标准的VRd/Rd剂量治疗；Isa-VRd患者接受了静脉注射Isa（第1周期，每周10 mg/kg；第2-17周期，每两周一次；后续周期，每四周一次）。

Patients with a frailty score of 0/1 were considered nonfrail; scores ≥2 were frail.

具有0/1分的脆弱性评分的患者被认为是非脆弱的；评分≥2的患者被认为是脆弱的。

Using this scoring, 26.7% of patients were frail (26.0% Isa-VRd; 27.6% VRd), and 72.0% non-frail (72.8% Isa-VRd; 70.7% VRd).

使用这种评分方法，26.7%的患者被认为是脆弱的（Isa-VRd组为26.0%；VRd组为27.6%），72.0%的患者被认为是非脆弱的（Isa-VRd组为72.8%；VRd组为70.7%）。

After a median follow-up of 59.7 months, Isa-VRd significantly improved progression-free survivalversus VRd in frail patients (hazard ratio[HR] =0.518; 95% confidence interval[CI]: 0.294-0.912; P=0.0227) and non-frail patients (HR=0.615; 95% CI: 0.419-0.903; P=0.0131).

中位随访时间为59.7个月后，Isa-VRd与VRd相比，在脆弱患者中显著改善了无进展生存期（风险比[HR] =0.518; 95% 置信区间[CI]: 0.294-0.912; P=0.0227）以及非脆弱患者（HR=0.615; 95% CI: 0.419-0.903; P=0.0131）。

Significantly more frail patients receiving Isa-VRd than VRd achieved minimal residual disease negativity and complete response (odds ratio=3.459; 95% CI: 1.495-8.006; P=0.0030 at 10-5 by next-generation sequencing).

接受Isa-VRd治疗的脆弱患者比接受VRd治疗的患者显著更多地实现了微小残留病灶阴性和完全缓解（比值比=3.459; 95% CI: 1.495-8.006; P=0.0030，通过下一代测序在10^-5水平上）。

Rates of treatment-emergent adverse events leading to definitive discontinuation were similar between both arms regardless of frailty status.

无论虚弱状态如何，导致治疗后不良事件最终停药的发生率在两组之间相似。

This post hoc subgroup analysis of the IMROZ trial demonstrated that Isa-VRd is an effective option with a manageable safety profile for frail patients with Ti NDMM (clinicaltrials gov.

这项IMROZ试验的事后亚组分析表明，Isa-VRd对于虚弱的Ti NDMM患者是一个有效且安全性可控的治疗选择（clinicaltrials gov）。

Identifier: NCT03319667).

注册号：NCT03319667）。