Clinical impact of [18F]FDG-PET/CT in ARI0002h treatment, a CAR-T against BCMA for relapsed/refractory multiple myeloma
Inés Zugasti, Marta Tormo-Ratera, Aina Oliver‐Caldés, Juan Carlos Soler-Perromat, Verónica González‐Calle, David F. Moreno, Valentín Cabañas, Nieves López‐Muñoz, Álvaro Bartolomé-Solanas, Marta Español‐Rego, Juan Luis Reguera, Laura Rosiñol, Lucía López‐Corral, Natalia Tovar, Luis Gerardo Rodríguez‐Lobato, R.M. Álvarez Pérez, Sara Varea, Eulàlia Olesti, Adolfo Gómez‐Grande, Laura Frutos, Pilar Tamayo, Manel Juan, José M. Moraleda, Álvaro Urbano-Ispizúa, Europa Azucena González‐Navarro, Joaquín Martínez‐López, María‐Victoria Mateos, Xavier Tomàs, Xavier Setoaín, Carlos Fernández de Larrea
Abstract
ABSTRACT: Multiple myeloma (MM) remains incurable, with poor outcomes in heavily pretreated patients. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment; however, outcomes after such therapy in patients with soft-tissue plasmacytomas and other bone lesions remain poorly understood. This study included 63 patients with relapsed/refractory MM treated either in the CARTBCMA-HCB-01 clinical trial (ARI0002h; academic B-cell maturation antigen [BCMA]-targeted CAR T-cell therapy) or in compassionate use. The aim was to evaluate the impact of soft-tissue involvement (extramedullary [EMD] and paraskeletal [PS] plasmacytomas) in response, survival and safety. Baseline [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) from 5 participating centers were reviewed centrally. Of 63 patients, 52.4% presented plasmacytomas at the time of inclusion (21 PS, exclusively; and 12 EMD). Per responses, there were no significant differences between patients with and without plasmacytomas. A correlation was present between International Myeloma Working Group responses and those obtained by [18F]FDG-PET/CT at day 100 (Bologna criteria). No differences were observed in progression-free survival (PFS) or overall survival (OS) between patients with or without plasmacytomas. However, both PFS and OS were significantly shorter in patients with EMD. Interestingly, [18F]FDG-PET/CT response assessed on day 100, in accordance with the Bologna criteria, was predictive of survival outcomes. A metabolic tumor volume of ≥25 cm3 at baseline [18F]FDG-PET/CT was associated with earlier disease progression and shorter OS. These results highlight the importance of EMD evaluation by [18F]FDG-PET/CT before and after CAR T-cell infusion. This trial was registered at www.ClinicalTrials.gov as #NCT04309981; and EudraCT, 2019-001472-11.