Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials
Lahuerta JJ (1), Paiva B (1), Vidriales MB (1), Cordón L (1), Cedena MT (1), Puig N (1), Martinez-Lopez J (1), Rosiñol L (1), Gutierrez NC (1), Martín-Ramos ML (1), Oriol A (1), Teruel AI (1), Echeveste MA (1), de Paz R (1), de Arriba F (1), Hernandez MT (1), Palomera L (1), Martinez R (1), Martin A (1), Alegre A (1), De la Rubia J (1), Orfao A (1), Mateos MV (1), Blade J (1), San-Miguel JF (1); GEM (Grupo Español de Mieloma)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) Cooperative Study Group. (1) 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.
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.
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%.
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.
CITATION J Clin Oncol. 2017 May 12:JCO2016692517. doi: 10.1200/JCO.2016.69.2517