Department of Haematology, Lille University Hospital, Lille.
Department of Hematology, University Hospital Hôtel-Dieu, Nantes.
Haematologica. 2024 Feb 1;109(2):604-616. doi: 10.3324/haematol.2023.283073.
Patients with multiple myeloma (MM) who experience early relapse within 12 months of therapy initiation are considered functional high-risk and represent an unmet need, needing better therapies to improve outcomes. The final IKEMA (clinicaltrials gov. identifier: NCT03275285) progression-free survival (PFS) analysis confirmed the significant PFS improvement reported at interim analysis with isatuximab (Isa) plus carfilzomib and dexamethasone (Kd; Isa-Kd) versus Kd in patients with relapsed MM (updated median PFS: 35.7 vs. 19.2 months; hazard ratio [HR] =0.58, 95% confidence interval [CI]: 0.42- 0.79). This IKEMA subgroup analysis examined efficacy and safety of Isa-Kd versus Kd in patients who experienced early (n=61 [Isa-Kd], n=46 [Kd]) vs. late relapse (n=104 [Isa-Kd], n=72 [Kd]). As expected, more aggressive features in baseline characteristics were observed in early relapse patients. Consistent with IKEMA overall population results, median PFS (early relapse: 24.7 vs. 17.2 months, HR=0.662, 95% CI: 0.407-1.077; late relapse: 42.7 vs. 21.9 months, HR=0.542, 95% CI: 0.355- 0.826), minimal residual disease negativity (MRD-) (early relapse: 24.6% vs. 15.2%; late relapse: 37.5% vs. 16.7%), and MRD- complete response (≥CR) rates (early relapse: 18.0% vs. 10.9%; late relapse: 30.8% vs. 13.9%) were higher with Isa-Kd versus Kd, respectively, in both early and late relapse patients. Grade ≥3, serious treatment-emergent adverse events, and death rates were higher in the late relapse Isa-Kd arm. However, the numbers of deaths were low and treatment exposure was significantly longer in Isa-Kd versus Kd late relapse patients. These results support the addition of Isa to Kd as standardof- care therapy for relapsed and/or refractory MM regardless of relapse timing.
在开始治疗后 12 个月内早期复发的多发性骨髓瘤 (MM) 患者被认为是功能高危患者，存在未满足的需求，需要更好的治疗方法来改善预后。最终的 IKEMA（clinicaltrials.gov 标识符：NCT03275285）无进展生存期 (PFS) 分析证实了伊沙佐米（Isa）联合卡非佐米和地塞米松（Kd；Isa-Kd）与 Kd 相比在复发 MM 患者中报告的显著 PFS 改善（更新的中位 PFS：35.7 与 19.2 个月；风险比 [HR]=0.58，95%置信区间 [CI]：0.42-0.79）。这项 IKEMA 亚组分析检查了 Isa-Kd 与 Kd 在早期（n=61 [Isa-Kd]，n=46 [Kd]）与晚期（n=104 [Isa-Kd]，n=72 [Kd]）复发患者中的疗效和安全性。正如预期的那样，早期复发患者的基线特征中观察到更具侵袭性的特征。与 IKEMA 总体人群结果一致，中位 PFS（早期复发：24.7 与 17.2 个月，HR=0.662，95%CI：0.407-1.077；晚期复发：42.7 与 21.9 个月，HR=0.542，95%CI：0.355-0.826）、微小残留病阴性（MRD-）（早期复发：24.6%与 15.2%；晚期复发：37.5%与 16.7%）和 MRD-完全缓解（≥CR）率（早期复发：18.0%与 10.9%；晚期复发：30.8%与 13.9%）均高于 Isa-Kd 与 Kd 相比，在早期和晚期复发患者中。晚期复发 Isa-Kd 组的 3 级及以上、严重治疗相关不良事件和死亡率更高。然而，死亡人数较低，Isa-Kd 与 Kd 晚期复发患者的治疗暴露时间明显更长。这些结果支持在复发和/或难治性 MM 中无论复发时间如何，将 Isa 联合 Kd 作为标准治疗方法。
