Turner Rose, Kalff Anna, Bergin Krystal, Gorniak Malgorzata, Fleming Shaun, Spencer Andrew
Department of Haematology, Alfred Health, Melbourne, VIC, Australia.
Department of Haematology, Alfred Health and Monash University, Melbourne, VIC, Australia.
Front Oncol. 2022 May 18;12:820605. doi: 10.3389/fonc.2022.820605. eCollection 2022.
Measurable residual disease (MRD) is being recognised as an optimal method for assessing depth of response, identifying higher risk of relapse, and guiding response-based treatment paradigms for multiple myeloma (MM). Although MRD negativity is increasingly replacing complete response as the surrogate endpoint in clinical trials, its role in real-world practice is less established. We retrospectively analyzed EuroFlow MRD results from patients with newly diagnosed MM (NDMM) who underwent bortezomib, cyclophosphamide and dexamethasone (VCD) induction and high dose melphalan conditioned autologous stem cell transplant (ASCT) at the Alfred Hospital between January 2016 and December 2020. Next generation flow MRD evaluation was performed 3 months following ASCT using the standardised EuroFlow platform. 112 patients with available MRD data were identified to have received VCD induction followed by ASCT. Post ASCT MRD was undetectable in 28.6% of patients. Those who achieved MRD negativity had significantly longer progression free survival (PFS) than those with persisting MRD (24-month PFS of 85% [95% CI: 72.4-99.9%] vs 63% [95% CI: 52.9-75.3%], p = 0.022). Maintenance therapy was associated with improved PFS regardless of MRD status (24-month PFS of 100% [95% CI: NA, p = 0.02] vs 73% [95% CI: 53.1-99.6%] in MRD negative, and 75% [95% CI: 64.2-88.6%] vs 36% [95% CI: 20.9-63.2%, p = 0.00015] in MRD positive patients). Results from this retrospective study of real-world practice demonstrate that Euroflow MRD analysis following standard VCD induction and ASCT in NDMM is feasible and allows more accurate prognostication, providing a platform for response adaptive therapies.
可测量残留病（MRD）正被公认为评估缓解深度、识别更高复发风险以及指导多发性骨髓瘤（MM）基于缓解的治疗模式的最佳方法。尽管MRD阴性在临床试验中越来越多地取代完全缓解作为替代终点，但其在实际临床实践中的作用仍不太明确。我们回顾性分析了2016年1月至2020年12月期间在阿尔弗雷德医院接受硼替佐米、环磷酰胺和地塞米松（VCD）诱导以及高剂量美法仑预处理自体干细胞移植（ASCT）的新诊断MM（NDMM）患者的欧洲流式细胞术MRD结果。在ASCT后3个月使用标准化的欧洲流式细胞术平台进行下一代流式MRD评估。确定112例有可用MRD数据的患者接受了VCD诱导，随后进行了ASCT。28.6%的患者ASCT后MRD检测不到。达到MRD阴性的患者无进展生存期（PFS）明显长于仍有MRD的患者（24个月PFS为85% [95% CI：72.4 - 99.9%] 对比63% [95% CI：52.9 - 75.3%]，p = 0.022）。无论MRD状态如何，维持治疗都与PFS改善相关（MRD阴性患者中24个月PFS为100% [95% CI：NA，p = 0.02] 对比73% [95% CI：53.1 - 99.6%]，MRD阳性患者中为75% [95% CI：64.2 - 88.6%] 对比36% [95% CI：20.9 - 63.2%，p = 0.00015]）。这项实际临床实践回顾性研究的结果表明，在NDMM中标准VCD诱导和ASCT后进行欧洲流式细胞术MRD分析是可行的，并且能实现更准确的预后评估，为适应性治疗提供了一个平台。
