Cancer Center Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra, Centro de Investigación Biomédica en Red de Cáncer (CIBER-ONC) number CB16/12/00369, Pamplona, Spain.
Department of Hematology, Hospital Universitario de Salamanca Hematología, Instituto de investigación Biomédica de Salamanca, Salamanca, Spain.
Blood. 2024 Feb 15;143(7):597-603. doi: 10.1182/blood.2023022083.
The role of measurable residual disease (MRD) negativity as a biomarker to stop treatment is being investigated in transplant-eligible patients with multiple myeloma (MM). Thus, it is important to identify risk factors of MRD resurgence and/or progressive disease (PD) among patients achieving undetectable MRD to avoid undertreating them. Here, we studied 267 newly diagnosed transplant-eligible patients with MM enrolled in the GEM2012MENOS65 and GEM2014MAIN clinical trials who achieved MRD negativity by next-generation flow cytometry. After a median follow-up of 73 months since the first MRD negative assessment, 111 of the 267 (42%) patients showed MRD resurgence and/or PD. The only prognostic factors at diagnosis that predicted MRD resurgence and/or PD were an International Staging System (ISS) 3 and the presence of ≥0.01% circulating tumor cells (CTCs). Failure to achieve MRD negativity after induction also predicted higher risk of MRD resurgence and/or PD. Patients having 0 vs 1 vs ≥2 risk factors (ISS 3, ≥0.01% CTCs, and late MRD negativity) showed 5-year rates of MRD resurgence and/or PD of 16%, 33%, and 57%, respectively (P < .001). Thus, these easily measurable risk factors could help refine the selection of patients for whom treatment cessation after MRD negativity is being investigated in clinical trials. This trial was registered at www.clinicaltrials.gov as NCT01916252 and NCT02406144.
在适合移植的多发性骨髓瘤（MM）患者中，作为停止治疗的生物标志物，可测量的残留疾病（MRD）阴性正在被研究。因此，重要的是要确定达到不可检测的 MRD 的患者中 MRD 复发和/或进展性疾病（PD）的风险因素，以避免对他们治疗不足。在这里，我们研究了 267 名新诊断的适合移植的 MM 患者，他们参加了 GEM2012MENOS65 和 GEM2014MAIN 临床试验，通过下一代流式细胞术达到了 MRD 阴性。自首次 MRD 阴性评估以来，中位随访 73 个月后，267 名患者中的 111 名（42%）出现了 MRD 复发和/或 PD。在诊断时唯一可预测 MRD 复发和/或 PD 的预后因素是国际分期系统（ISS）3 和存在≥0.01%循环肿瘤细胞（CTC）。诱导后未能达到 MRD 阴性也预示着更高的 MRD 复发和/或 PD 风险。MRD 阴性后没有达到 0、1 或≥2 个风险因素（ISS 3、≥0.01%CTC 和晚期 MRD 阴性）的患者，5 年的 MRD 复发和/或 PD 率分别为 16%、33%和 57%（P<0.001）。因此，这些易于测量的风险因素可以帮助完善临床试验中对 MRD 阴性后停止治疗的患者选择。这项试验在 www.clinicaltrials.gov 上注册，编号为 NCT01916252 和 NCT02406144。
