Multiple Myeloma and Amyloidosis Program, Columbia University Irving Medical Center, New York, New York.
Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan.
Cancer. 2022 Jun 15;128(12):2288-2297. doi: 10.1002/cncr.34211. Epub 2022 Apr 4.
Despite routine evaluation of cytogenetics in myeloma, little is known regarding the impact of high-dose therapy (HDT) consolidation on overall survival (OS) or progression-free survival (PFS) in patients who have high-risk cytogenetics. The authors performed a meta-analysis of randomized controlled trials (RCTs) to assess the heterogeneity of HDT efficacy according to cytogenetic risk.
All RCTs in patients who had newly diagnosed myeloma from 2000 to 2021 that compared upfront HDT versus standard-dose therapy (SDT) consolidation were included. The primary objective was to assess the difference in HDT efficacy between standard-risk and high-risk cytogenetics in terms of the OS or PFS log(hazard ratio) (HR). The pooled OS and PFS HR was calculated according to cytogenetic-risk subgroup using a random-effects model, and heterogeneity (I ) (the percentage of total observed variability explained by between-study differences) was assessed using an interaction test.
After screening 3307 citations, 6 RCTs were included for PFS analysis, and 4 were included for OS analysis. The median follow-up ranged from 3.1 to 7.8 years. The pooled OS HR for HDT versus SDT consolidation in patients with standard-risk and high-risk cytogenetics was 0.90 (95% confidence interval [CI], 0.70-1.17; I = 0%) and 0.66 (95% CI, 0.45-0.97; I = 0%), respectively. The difference in HDT efficacy in terms of OS between standard-risk and high-risk patients was statistically significant in favor of the high-risk group (P for interaction = .03). The pooled PFS HR for HDT versus SDT was 0.65 (95% CI 0.56-0.76; I = 0%) versus 0.52 (95% CI, 0.33-0.83; I = 55%), respectively. The difference in HDT efficacy in terms of PFS between standard-risk and high-risk patients was not significant (P for interaction = .25).
The magnitude of OS benefit with upfront HDT is cytogenetics-dependent. Patients with high-risk cytogenetics should preferably receive upfront rather than delayed HDT consolidation.
Upfront autologous stem cell transplantation improves overall survival in patients with newly diagnosed myeloma harboring high-risk cytogenetics.
尽管多发性骨髓瘤患者的细胞遗传学常规评估，但对于具有高危细胞遗传学的患者，高剂量治疗（HDT）巩固治疗对总生存期（OS）或无进展生存期（PFS）的影响知之甚少。作者对 2000 年至 2021 年间新诊断为多发性骨髓瘤的患者进行了随机对照试验（RCT）的荟萃分析，以根据细胞遗传学风险评估 HDT 疗效的异质性。
纳入了比较初始 HDT 与标准剂量治疗（SDT）巩固治疗的新诊断多发性骨髓瘤患者的所有 RCT。主要目的是根据 OS 或 PFS 对数（危险比）（HR）评估标准风险和高危细胞遗传学之间 HDT 疗效的差异。根据细胞遗传风险亚组使用随机效应模型计算合并 OS 和 PFS HR，并使用交互检验评估异质性（I）（研究间差异解释的总观察变异性的百分比）。
在筛选了 3307 篇参考文献后，纳入了 6 项 RCT 进行 PFS 分析，4 项 RCT 进行 OS 分析。中位随访时间范围为 3.1 至 7.8 年。标准风险和高危细胞遗传学患者中 HDT 与 SDT 巩固治疗的合并 OS HR 分别为 0.90（95%置信区间 [CI]，0.70-1.17；I = 0%）和 0.66（95%CI，0.45-0.97；I = 0%）。高危患者的 OS 方面 HDT 疗效差异具有统计学意义，支持高危组（交互检验 P =.03）。HDT 与 SDT 的合并 PFS HR 分别为 0.65（95%CI 0.56-0.76；I = 0%）和 0.52（95%CI，0.33-0.83；I = 55%）。标准风险和高危患者的 PFS 方面 HDT 疗效差异无统计学意义（交互检验 P =.25）。
初始 HDT 的 OS 获益程度取决于细胞遗传学。具有高危细胞遗传学的患者最好接受初始而非延迟的 HDT 巩固治疗。
新诊断多发性骨髓瘤患者接受初始自体干细胞移植可提高总生存期。
