2026-08-05T15:15:49Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/231252024-11-28T16:11:53Zcom_20.500.12105_2173com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19597col_20.500.12105_16938col_20.500.12105_16960
Repisalud author Jiménez-Ubieto, Ana author Martín-Muñoz, Alejandro author Poza, María author Dorado, Sara author García-Ortiz, Almudena author Revilla, Enrique author Sarandeses, Pilar author Ruiz-Heredia, Yanira author Baumann, Tycho author Rodríguez, Antonia author Calbacho, María author Sánchez, Pilar Martínez author Pina, José María Sánchez author García-Sancho, Alejandro Martín author Figaredo, Gloria author Rufián, Laura author Rodríguez, Margarita author Carneros, Laura author Martínez-Laperche, Carolina author Bastos-Oreiro, Mariana author Wang, Chongwu author Cedena, María-Teresa author Rapado, Inmaculada author de Toledo, Paula author Gallardo, Miguel author Valeri, Antonio author Ayala, Rosa author Martinez-Lopez, Joaquin author Barrio, Santiago funder Instituto de Salud Carlos III funder CRIS contra el Cáncer funder Unión Europea 2024-09-16T08:17:16Z 2024-09-16T08:17:16Z 2023 Front Immunol . 2023 :14:1188818. 10.3389/fimmu.2023.1188818 1664-3224 Frontiers in immunology 37342332 https://hdl.handle.net/20.500.12105/23125 BACKGROUND: CART therapy has produced a paradigm shift in the treatment of relapsing FL patients. Strategies to optimize disease surveillance after these therapies are increasingly necessary. This study explores the potential value of ctDNA monitoring with an innovative signature of personalized trackable mutations. METHOD: Eleven FL patients treated with anti-CD19 CAR T-cell therapy were included. One did not respond and was excluded. Genomic profiling was performed before starting lymphodepleting chemotherapy to identify somatic mutations suitable for LiqBio-MRD monitoring. The dynamics of the baseline mutations (4.5 per patient) were further analyzed on 59 cfDNA follow-up samples. PET/CT examinations were performed on days +90, +180, +365, and every six months until disease progression or death. RESULTS: After a median follow-up of 36 months, all patients achieved a CR as the best response. Two patients progressed. The most frequently mutated genes were CREBBP, KMT2D and EP300. Simultaneous analysis of ctDNA and PET/CT was available for 18 time-points. When PET/CT was positive, two out of four ctDNA samples were LiqBio-MRD negative. These two negative samples corresponded to women with a unique mesenteric mass in two evaluations and never relapsed. Meanwhile, 14 PET/CT negative images were mutation-free based on our LiqBio-MRD analysis (100%). None of the patients had a negative LiqBio-MRD test by day +7. Interestingly, all durably responding patients had undetectable ctDNA at or around three months after infusion. Two patients presented discordant results by PET/CT and ctDNA levels. No progression was confirmed in these cases. All the progressing patients were LiqBio-MRD positive before progression. CONCLUSION: This is a proof-of-principle for using ctDNA to monitor response to CAR T-cell therapy in FL. Our results confirm that a non-invasive liquid biopsy MRD analysis may correlate with response and could be used to monitor response. Harmonized definitions of ctDNA molecular response and pinpointing the optimal timing for assessing ctDNA responses are necessary for this setting. If using ctDNA analysis, we suggest restricting follow-up PET/CT in CR patients to a clinical suspicion of relapse, to avoid false-positive results. eng Personalized monitoring of circulating tumor DNA with a specific signature of trackable mutations after chimeric antigen receptor T-cell therapy in follicular lymphoma patients research article