Ficek Joseph, Kalaitzaki Eleftheria, Yuan Shuai Sammy, Tosolini Alessandra, Du Ling, Kremer Brandon E, Davy Katherine, Zhou Helen, Chen Tai-Tsang
Oncology Statistics, GSK, Collegeville, PA.
Oncology Statistics, GSK, Stevenage, UK.
Clin Lymphoma Myeloma Leuk. 2023 May;23(5):e213-e221. doi: 10.1016/j.clml.2023.02.005. Epub 2023 Feb 21.
Current frontline therapies for newly diagnosed multiple myeloma patients have significantly prolonged progression-free survival (PFS). This has led to interest in minimal residual disease negativity (MRDng) as an efficacy-response biomarker and possible surrogate endpoint. A meta-analysis was conducted to explore the surrogacy of MRD for PFS and quantify the relationship between MRDng rates and PFS at the trial level. A systematic search was conducted on phase II and III trials reporting MRDng rates along with median PFS (mPFS) or PFS hazard ratios (HR). Weighted linear regressions were conducted relating mPFS to MRDng rates, and relating PFS HRs to either odds ratios (OR) or rate differences (RD) for MRDng in comparative trials. A total of 14 trials were available for the mPFS analysis. log(MRDng rate) was moderately associated with log (mPFS), with a slope of β = 0.37 (95% CI, 0.26 to 0.48) and R = 0.62. A total of 13 trials were available for the PFS HR analysis. Treatment effects on MRDng rates were correlated with the corresponding effects on PFS: log (PFS HR) and log (MRDng OR) had a moderate association with β = -0.36 (95% CI, -0.56 to -0.17) and R = 0.53 (95% CI, 0.21 to 0.77); log (PFS HR) and the MRDng RD had a stronger association with slope β = -0.03 (95% CI, -0.04 to -0.02) and R = 0.67 (95% CI, 0.31 to 0.86). MRDng rates moderately associate with PFS outcomes. MRDng RDs are more strongly associated with HRs than MRDng ORs, with evidence suggestive of potential surrogacy.
目前，针对新诊断的多发性骨髓瘤患者的一线治疗已显著延长了无进展生存期（PFS）。这引发了人们对微小残留病阴性（MRDng）作为疗效反应生物标志物和可能的替代终点的兴趣。进行了一项荟萃分析，以探讨MRD对PFS的替代作用，并在试验层面量化MRDng率与PFS之间的关系。对报告了MRDng率以及中位PFS（mPFS）或PFS风险比（HR）的II期和III期试验进行了系统检索。进行了加权线性回归，将mPFS与MRDng率相关联，并将比较试验中PFS的HR与MRDng的比值比（OR）或率差（RD）相关联。共有14项试验可用于mPFS分析。log（MRDng率）与log（mPFS）呈中度相关，斜率β = 0.37（95%CI，0.26至0.48），R = 0.62。共有13项试验可用于PFS HR分析。对MRDng率的治疗效果与对PFS的相应效果相关：log（PFS HR）与log（MRDng OR）呈中度相关，β = -0.36（95%CI，-0.56至-0.17），R = 0.53（95%CI，0.21至0.77）；log（PFS HR）与MRDng RD的相关性更强，斜率β = -0.03（95%CI，-0.04至-0.02），R = 0.67（95%CI，0.31至0.86）。MRDng率与PFS结果呈中度相关。MRDng的RD与HR的相关性比MRDng的OR更强，有证据表明存在潜在的替代作用。
