Minimally Invasive Assessment of Peripheral Residual Disease During Maintenance or Observation in Transplant-Eligible Patients With Multiple Myeloma
Authors: Marta Lasa, Laura Notarfranchi, Cristina Agullo, Carmen Gonzalez, Sergio Castro, Jose J. Perez, Leire Burgos, Camila Guerrero, Maria Jose Calasanz, Juan Flores-Montero, Albert Oriol, Joan Bargay, Rafael Rios, Valentin Cabañas, Carmen Cabrera, Rafael Martinez-Martinez, Cristina Encinas, Felipe De Arriba, Miguel-Teodoro Hernandez, Luis Palomera, Alberto Orfao, Joaquin Martinez-Lopez, Maria-Victoria Mateos, Jesus San-Miguel, Juan Jose Lahuerta, Laura Rosiñol, Joan Blade, Maria Teresa Cedena, Noemi Puig, Bruno Paiva, María Casanova, Carmen Couto, Estrella Carrillo, Esther González, Ana Pilar González, Antonia Sampol, Alexia Suárez, Carmen Montes, Mª del Carmen Calle, Luís Felipe Casado, Dunia de Miguel, Ángela Ibáñez, Jorge Labrador, Aránzazu García, Fernando Escalante, Carlos Aguilar, Lourdes Escoda, Ana María Sureda, Cristina Motlló, Yolanda González, Eugenia Monreal, Juan Alfonso Soler, Miquel Granell, Elena Cabezudo, Josep Mª Martí, Antonio García, Mercedes Gironella, Ana Dios, José Ángel Méndez, Marta Sonia González, Mª José Nájera, Francisco Javier Peñalver, Pilar Bravo, José Ángel Hernández, Jaime Pérez de Oteyza, Rebeca Iglesias del Barrio, Ana López de la Guía, Adrián Alegre, Isabel Krsnik, Elena Ruíz, Mª Jesús Blanchard, Belén Íñigo, Eugenio Giménez, Rosalía Riaza, Elena Prieto, Marta Romera, Jose Mª Moraleda, Felipe Prósper, Jose Mª Arguiñano, María Puente, Xabier Gutiérrez, Ana Isabel Teruel, Paz Rivas, Isidro Jarque, Ángel Fernández, Amparo Santamaría, Carmen Martínez
Journal: Journal of Clinical Oncology (2024)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In multiple myeloma (MM), measurable residual disease (MRD) is assessed in bone marrow (BM). However, less invasive evaluation of peripheral residual disease (PRD) in blood could be advantageous and less cumbersome. We investigated the prognostic value of PRD monitoring after 24 cycles of maintenance in 138 transplant-eligible patients with MM enrolled in the GEM2012MENOS65/GEM2014MAIN clinical trials. PRD was assessed using next-generation flow (NGF) and mass spectrometry (MS). Positive PRD by NGF in 16/138 (11.5%) patients was associated with a 13-fold increased risk of progression and/or death; median progression-free survival (PFS) and overall survival (OS) were 2.5 and 47 months, respectively. Considering patients' MRD status in BM as the reference, PRD detection using NGF showed positive and negative predictive values of 100% and 73%, respectively. Presence of PRD helped identifying patients at risk of imminent progression among those with positive MRD in BM. Patients with undetectable PRD according to both NGF and MS showed 2-year PFS and OS rates of 97% and 100%, respectively. In multivariate analyses including the Revised International Staging System and the complete remission status, only MRD in BM and PRD by NGF showed independent prognostic value for PFS. This study supports the use of less invasive PRD monitoring during maintenance or observation in transplant-eligible patients with MM.