Department of Medicine, University of California, San Francisco, CA.
Translational Genomics Research Institute, City of Hope Cancer Center, Phoenix, AZ.
Blood Adv. 2022 Aug 9;6(15):4506-4515. doi: 10.1182/bloodadvances.2021006713.
The IKEMA study (Randomized, Open Label, Multicenter Study Assessing the Clinical Benefit of Isatuximab Combined With Carfilzomib [Kyprolis®] and Dexamethasone Versus Carfilzomib With Dexamethasone in Patients With Relapse and/or Refractory Multiple Myeloma Previously Treated With 1 to 3 Prior Lines; #NCT03275285) was a randomized, open-label, multicenter phase 3 study investigating isatuximab plus carfilzomib and dexamethasone (Isa-Kd) vs Kd in patients with relapsed multiple myeloma. This subanalysis analyzed the depth of response of Isa-Kd vs Kd. The primary end point was progression-free survival (PFS); secondary end points included overall response rate, very good partial response or better (≥VGPR) rate, complete response (CR) rate, and minimal residual disease (MRD) negativity rate (assessed in patients with ≥VGPR by next-generation sequencing at a 10-5 sensitivity level). At a median follow-up of 20.7 months, deeper responses were observed in the Isa-Kd arm vs the Kd arm, with ≥VGPR 72.6% vs 56.1% and CR of 39.7% vs 27.6%, respectively. MRD negativity occurred in 53 (29.6%) of 179 patients in the Isa-Kd arm vs 16 (13.0%) of 123 patients in the Kd arm, with 20.1% (Isa-Kd, 36 of 179 patients) vs 10.6% (Kd, 13 of 123 patients) reaching MRD-negative CR status. Achieving MRD negativity resulted in better PFS in both arms. A positive PFS treatment effect was seen with Isa-Kd in both MRD-negative patients (hazard ratio, 0.578; 95% CI, 0.052-6.405) and MRD-positive patients (hazard ratio, 0.670; 95% CI, 0.452-0.993). Exploratory analysis indicates that both current CR and MRD-negative CR rates are underestimated due to M-protein interference (potential adjusted CR rate, 45.8%; potential adjusted MRD-negative CR rate, 24.0%). In conclusion, there was a clinically meaningful improvement in depth of response with Isa-Kd. The CR rate in Isa-Kd was 39.7%. Mass spectrometry suggests that the potential adjusted CR rate could reach an unprecedented 45.8% of patients treated with Isa-Kd.
IKEMA 研究（随机、开放标签、多中心研究，评估伊沙佐米联合卡非佐米[Kyprolis®]和地塞米松与卡非佐米联合地塞米松在先前接受 1 至 3 线治疗的复发和/或难治性多发性骨髓瘤患者中的临床获益；#NCT03275285）是一项随机、开放标签、多中心的 3 期研究，旨在评估伊沙佐米联合卡非佐米和地塞米松（Isa-Kd）与 Kd 在复发多发性骨髓瘤患者中的疗效。这项亚分析分析了 Isa-Kd 与 Kd 的反应深度。主要终点是无进展生存期（PFS）；次要终点包括总缓解率、非常好的部分缓解或更好（≥VGPR）率、完全缓解（CR）率和微小残留疾病（MRD）阴性率（通过下一代测序在 10-5 灵敏度水平评估≥VGPR 的患者）。在中位随访 20.7 个月时，Isa-Kd 组的反应深度大于 Kd 组，≥VGPR 率分别为 72.6%和 56.1%，CR 率分别为 39.7%和 27.6%。MRD 阴性发生在 Isa-Kd 组的 179 名患者中的 53 名（29.6%）和 Kd 组的 123 名患者中的 16 名（13.0%），20.1%（Isa-Kd，179 名患者中的 36 名）和 10.6%（Kd，123 名患者中的 13 名）达到了 MRD 阴性 CR 状态。在两个治疗组中，达到 MRD 阴性均可改善 PFS。在两个治疗组中，MRD 阴性患者（风险比，0.578；95%CI，0.052-6.405）和 MRD 阳性患者（风险比，0.670；95%CI，0.452-0.993）的 PFS 均有阳性治疗效果。探索性分析表明，由于 M 蛋白干扰（潜在调整后的 CR 率，45.8%；潜在调整后的 MRD 阴性 CR 率，24.0%），目前的 CR 率和 MRD 阴性 CR 率均被低估。总之，Isa-Kd 可显著提高反应深度。Isa-Kd 的 CR 率为 39.7%。质谱分析提示，Isa-Kd 治疗的潜在调整后的 CR 率可能达到前所未有的 45.8%。
