Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic.
4th Department of Internal Medicine - Hematology, Faculty Hospital and Charles University in Hradec Kralove, Hradec Kralove, Czech Republic.
BMC Cancer. 2021 Jan 15;21(1):73. doi: 10.1186/s12885-020-07732-1.
We have performed a head to head comparison of all-oral triplet combination of ixazomib, lenalidomide and dexamethasone (IRD) versus lenalidomide and dexamethasone (RD) in patients with relapsed and refractory multiple myeloma (RRMM) in the routine clinical practice.
A total of 344 patients treated with IRD (N = 127) or RD (N = 217) were selected for analysis from the Czech Registry of Monoclonal Gammopathies (RMG). Descriptive statistics were used to assess patient's characteristics associated with the respective therapy. The primary endpoint was progression free survival (PFS), secondary end points included response rates and overall survival (OS). Survival endpoints were plotted using Kaplan-Meier methodology at 95% Greenwood confidence interval. Univariable and multivariable Cox proportional hazards models were used to evaluate the effect of treatment regimens and the significance of uneven variables. Statistical tests were performed at significance level 0.05.
In the whole cohort, median PFS for IRD was 17.5 and for RD was 11.5 months favoring the all-oral triplet, p = 0.005; in patients within relapse 1-3, the median PFS was 23.1 vs 11.6 months, p = 0.001. The hazard ratio for PFS was 0.67 (95% confidence interval [CI] 0.51-0.89, p = 0.006). The PFS advantage translated into improved OS for patients treated with IRD, median 36.6 months vs 26.0 months (p = 0.008). The overall response rate (ORR) was 73.0% in the IRD group vs 66.2% in the RD group with a complete response rate (CR) of 11.1% vs 8.8%, and very good partial response (VGPR) 22.2% vs 13.9%, IRD vs RD respectively. The IRD regimen was most beneficial in patients ≤75 years with ISS I, II, and in the first and second relapse. Patients with the presence of extramedullary disease did not benefit from IRD treatment (median PFS 6.5 months). Both regimens were well tolerated, and the incidence of total as well as grade 3/4 toxicities was comparable.
Our analysis confirms the results of the TOURMALINE-MM1 study and shows benefit of all-oral triplet IRD treatment versus RD doublet. It demonstrates that the addition of ixazomib to RD improves key survival endpoints in patients with RRMM in a routine clinical setting.
我们在常规临床实践中对复发/难治性多发性骨髓瘤（RRMM）患者进行了伊沙佐米、来那度胺和地塞米松（IRD）与来那度胺和地塞米松（RD）的头对头比较。
从捷克骨髓瘤登记处（RMG）中选择了 344 名接受 IRD（N=127）或 RD（N=217）治疗的患者进行分析。使用描述性统计数据评估与各自治疗相关的患者特征。主要终点是无进展生存期（PFS），次要终点包括反应率和总生存期（OS）。使用 Kaplan-Meier 方法在 95%的 Greenwood 置信区间内绘制生存终点。使用单变量和多变量 Cox 比例风险模型评估治疗方案的效果和不均匀变量的意义。统计检验的显著性水平为 0.05。
在整个队列中，IRD 的中位 PFS 为 17.5 个月，RD 为 11.5 个月，支持全口服三联疗法，p=0.005；在复发 1-3 个月的患者中，中位 PFS 为 23.1 个月 vs 11.6 个月，p=0.001。PFS 的风险比为 0.67（95%置信区间 [CI] 0.51-0.89，p=0.006）。IRD 治疗的 PFS 优势转化为患者 OS 的改善，中位 36.6 个月 vs 26.0 个月（p=0.008）。IRD 组的总缓解率（ORR）为 73.0%，RD 组为 66.2%，完全缓解率（CR）为 11.1%，RD 组为 8.8%，非常好的部分缓解（VGPR）为 22.2%，RD 组为 13.9%。IRD 方案在≤75 岁、ISS I、II 以及第一次和第二次复发的患者中最有益。有髓外疾病的患者不能从 IRD 治疗中获益（中位 PFS 6.5 个月）。两种方案均耐受良好，总毒性和 3/4 级毒性的发生率相当。
我们的分析证实了 TOURMALINE-MM1 研究的结果，并表明全口服三联 IRD 治疗优于 RD 双联治疗。它表明，在常规临床环境中，在 RD 中添加伊沙佐米可改善 RRMM 患者的关键生存终点。
