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在复发多发性骨髓瘤中,对伊沙妥昔单抗联合卡非佐米和地塞米松与达雷妥尤单抗联合来那度胺和地塞米松的匹配调整间接比较。

Matching-adjusted indirect comparison of isatuximab plus carfilzomib and dexamethasone with daratumumab plus lenalidomide and dexamethasone in relapsed multiple myeloma.

机构信息

Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Sanofi, Cambridge, Massachusetts, USA.

出版信息

Cancer Med. 2023 Apr;12(7):8005-8017. doi: 10.1002/cam4.5584. Epub 2023 Feb 1.

Abstract

BACKGOUND

Lenalidomide-based regimens are commonly used for early relapse in patients with relapsed and/or refractory multiple myeloma (RRMM) receiving at least one prior line of therapy. In the absence of head-to-head comparison, matching-adjusted indirect comparison (MAIC) was conducted to demonstrate efficacy and safety of isatuximab+carfilzomib+dexamethasone (Isa-Kd) versus daratumumab + lenalidomide + dexamethasone (Dara-Rd) in RRMM.

METHODS

Patient-level data from IKEMA trial (Isa-Kd, n = 179) were matched to aggregate data from POLLUX (Dara-Rd, n = 286). Hazard ratios (HR) and 95% confidence intervals (CI) for progression-free survival (PFS) and overall survival (OS) were generated by weighted Cox proportional hazard models. Odds ratios (OR), 95% CI, and p-value were calculated for ≥very good partial response (≥VGPR) and treatment-emergent adverse events (TEAEs).

RESULTS

After matching, no significant differences were observed between Isa-Kd and Dara-Rd in baseline characteristics except for patients with >3 prior lines (0.0% vs. 4.9%). Isa-Kd showed significantly better PFS (HR [95% CI]: 0.46 [0.24-0.86]; p = 0.0155), statistically non-significant improvement favoring Isa-Kd in OS (0.47 [0.20-1.09]; 0.0798), and ≥VGPR (OR [95% CI]: 1.53 [0.89-2.64]; p = 0.1252) than Dara-Rd. Odds of occurrence were significantly lower for some all-grade and grade 3/4 TEAEs with Isa-Kd than Dara-Rd.

CONCLUSION

These results support Isa-Kd as an efficacious treatment for early relapse in non-lenalidomide refractory patients.

摘要

背景

在接受至少一线治疗的复发/难治性多发性骨髓瘤(RRMM)患者中,基于来那度胺的方案常用于早期复发。在没有头对头比较的情况下,采用匹配调整间接比较(MAIC)来证明伊沙佐米+卡非佐米+地塞米松(Isa-Kd)与达雷妥尤单抗+来那度胺+地塞米松(Dara-Rd)在 RRMM 中的疗效和安全性。

方法

从 IKEMA 试验(Isa-Kd,n=179)的患者水平数据中进行匹配,汇总来自 POLLUX(Dara-Rd,n=286)的数据。通过加权 Cox 比例风险模型生成无进展生存期(PFS)和总生存期(OS)的风险比(HR)和 95%置信区间(CI)。计算≥非常好的部分缓解(≥VGPR)和治疗中出现的不良事件(TEAEs)的比值比(OR)、95%CI 和 p 值。

结果

匹配后,除了有>3 条既往治疗线的患者(0.0%对 4.9%)外,Isa-Kd 和 Dara-Rd 在基线特征方面没有显著差异。Isa-Kd 表现出显著更好的 PFS(HR [95%CI]:0.46 [0.24-0.86];p=0.0155),OS 方面有统计学上非显著的获益倾向于 Isa-Kd(0.47 [0.20-1.09];0.0798),以及≥VGPR(OR [95%CI]:1.53 [0.89-2.64];p=0.1252)。与 Dara-Rd 相比,Isa-Kd 发生某些全级和 3/4 级 TEAEs 的可能性显著降低。

结论

这些结果支持 Isa-Kd 作为非来那度胺难治性患者早期复发的有效治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b22e/10134287/b91b4f95a6ea/CAM4-12-8005-g002.jpg

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