Lahuerta Juan-Jose, Paiva Bruno, Vidriales Maria-Belen, Cordón Lourdes, Cedena Maria-Teresa, Puig Noemi, Martinez-Lopez Joaquin, Rosiñol Laura, Gutierrez Norma C, Martín-Ramos María-Luisa, Oriol Albert, Teruel Ana-Isabel, Echeveste María-Asunción, de Paz Raquel, de Arriba Felipe, Hernandez Miguel T, Palomera Luis, Martinez Rafael, Martin Alejandro, Alegre Adrian, De la Rubia Javier, Orfao Alberto, Mateos María-Victoria, Blade Joan, San-Miguel Jesus F
Juan-Jose Lahuerta, Maria-Teresa Cedena, Joaquin Martinez-Lopez, and María-Luisa Martín-Ramos, Hospital 12 de Octubre, CIBERONC; Raquel de Paz, Hospital Universitario La Paz; Rafael Martinez, Hospital Clínico San Carlos; Adrian Alegre, Hospital Universitario La Princesa, Madrid; Bruno Paiva and Jesus F. San-Miguel, Clinica Universidad de Navarra, Centro de Investigación Médica Aplicada (CIMA), IDISNA, CIBERONC, Pamplona; Laura Rosiñol, and Joan Blade, Hospital Clínic de Barcelona, Barcelona; Maria-Belen Vidriales, Noemi Puig, Norma C. Gutierrez, Alejandro Martin, and María-Victoria Mateos, Hospital Universitario de Salamanca Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), CIBERONC; Alberto Orfao, Servicio General de Citometría-NUCLEOS, Centro de Investigación del Cancer (IBMCC-USAL, CSIC), IBSAL and Department of Medicine, Universidad de Salamanca, CIBERONC, Salamanca; Lourdes Cordón and Javier De la Rubia, Hospital Universitario y Politécnico La Fe; Ana-Isabel Teruel, Hospital Clínico de Valencia, Valencia; Albert Oriol, Hospital Germans Trias i Pujol, Badalona; María-Asunción Echeveste, Hospital de Donostia, San Sebastian; Felipe de Arriba, Hospital Morales Meseguer, Murcia; Miguel T. Hernandez, Hospital Universitario de Canarias, Tenerife; Luis Palomera, Hospital Universitario Lozano Blesa, Zaragoza, Spain.
J Clin Oncol. 2017 Sep 1;35(25):2900-2910. doi: 10.1200/JCO.2016.69.2517. Epub 2017 May 12.
Purpose To perform a critical analysis on the impact of depth of response in newly diagnosed multiple myeloma (MM). Patients and Methods Data were analyzed from 609 patients who were enrolled in the GEM (Grupo Español de Mieloma) 2000 and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65 clinical trial for elderly patients with MM who had minimal residual disease (MRD) assessments 9 months after study enrollment. Median follow-up of the series was 71 months. Results Achievement of complete remission (CR) in the absence of MRD negativity was not associated with prolonged progression-free survival (PFS) and overall survival (OS) compared with near-CR or partial response (median PFS, 27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months, respectively). MRD-negative status was strongly associated with prolonged PFS (median, 63 months; P < .001) and OS (median not reached; P < .001) overall and in subgroups defined by prior transplantation, disease stage, and cytogenetics, with prognostic superiority of MRD negativity versus CR particularly evident in patients with high-risk cytogenetics. Accordingly, Harrell C statistics showed higher discrimination for both PFS and OS in Cox models that included MRD (as opposed to CR) for response assessment. Superior MRD-negative rates after different induction regimens anticipated prolonged PFS. Among 34 MRD-negative patients with MM and a phenotypic pattern of bone marrow involvement similar to monoclonal gammopathy of undetermined significance at diagnosis, the probability of "operational cure" was high; median PFS was 12 years, and the 10-year OS rate was 94%. Conclusion Our results demonstrate that MRD-negative status surpasses the prognostic value of CR achievement for PFS and OS across the disease spectrum, regardless of the type of treatment or patient risk group. MRD negativity should be considered as one of the most relevant end points for transplant-eligible and elderly fit patients with MM.
目的 对新诊断的多发性骨髓瘤（MM）中缓解深度的影响进行批判性分析。患者与方法 分析了609例患者的数据，这些患者纳入了GEM（西班牙骨髓瘤研究组）2000和GEM2005MENOS65研究，针对适合移植的MM患者，以及GEM2010MAS65临床试验，针对有微小残留病（MRD）评估的老年MM患者，评估在研究入组9个月后进行。该系列的中位随访时间为71个月。结果 与接近完全缓解（CR）或部分缓解相比，在无MRD阴性的情况下实现完全缓解与无进展生存期（PFS）和总生存期（OS）的延长无关（中位PFS分别为27、27和29个月；中位OS分别为59、64和65个月）。MRD阴性状态与PFS延长（中位，63个月；P <.001）和OS延长（中位未达到；P <.001）总体相关，并且在根据先前移植、疾病分期和细胞遗传学定义的亚组中也相关，MRD阴性相对于CR的预后优势在高危细胞遗传学患者中尤为明显。因此，Harrell C统计显示，在用于反应评估的Cox模型中，包括MRD（而非CR）时，对PFS和OS的区分度更高。不同诱导方案后较高的MRD阴性率预示着PFS延长。在34例MM且骨髓受累表型模式类似于诊断时意义未明的单克隆丙种球蛋白病的MRD阴性患者中，“手术治愈”的概率很高；中位PFS为12年，10年OS率为94%。结论 我们的结果表明，无论治疗类型或患者风险组如何，MRD阴性状态在整个疾病谱中对于PFS和OS的预后价值超过了实现CR的预后价值。对于适合移植和身体状况良好的老年MM患者，MRD阴性应被视为最相关的终点之一。
