Combining CAR T-Cell Therapy and Nivolumab to Overcome Immune Resistance in THRLBCL: A Case Report
Year: 2025
Type: article
Study design: Case Report
Abstract: T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare, aggressive subtype of diffuse large B-cell lymphoma characterized by a profoundly immunosuppressive tumor microenvironment. PD-L1 overexpression by tumor cells is a recognized immune escape mechanism and may underlie resistance to cellular therapies, including CAR T-cell therapy. We report a case of a 29-year-old woman with refractory stage IV-B THRLBCL treated with anti-CD19 CAR T-cell therapy (varnimcabtagene autoleucel), who achieved an initial response (day +28) but experienced disease progression by day +100 despite robust CAR T-cell expansion. Peripheral blood analysis revealed persistent absolute B-cell aplasia, while bone marrow biopsy confirmed CD19-positive disease. Comparative immunohistochemistry demonstrated markedly increased PD-L1 expression in post-CAR T-cell samples, suggesting adaptive immune resistance via PD-1/PD-L1-mediated CAR T-cell inhibition. Nivolumab was initiated at month +4 to overcome this checkpoint-mediated resistance. Notably, a complete metabolic response was documented on PET/CT after four doses of nivolumab (month +6). The patient remains in sustained remission, with persistent B-cell aplasia, four years post-intervention. This case provides clinical and pathological evidence supporting the use of immune checkpoint blockade to rescue CAR T-cell efficacy, highlighting the potential of this synergistic approach in THRLBCL and possibly other B-cell malignancies exhibiting similar immune evasion.
DOI: 10.3390/ijms26199265
Authors: Daniel Munarriz, Oriana López-Godino, Nuria Martinez-Cibrian, Nil Albiol, Helena Brillembourg, Sergio Navarro-Velázquez, Marta Español-Rego, Sebastián Casanueva, Lucía García-Tomás, Guillermo Muñoz-Sanchez, Leticia Alserawan, Daniel Benitez-Ribas, Laura Magnano, Juan Gonzalo Correa, Andrea Rivero, Pablo Mozas, Eva Gine, Luis Gerardo Rodríguez-Lobato, Alexandra Martínez-Roca, Mercedes Montoro-Lorite, Pilar Ayora, Jordi Esteve, Laura Frutos, Olga Balagué-Ponz, Alvaro Urbano-Ispizua, Europa Azucena González-Navarro, Manel Juan, Julio Delgado, Valentín Ortiz-Maldonado
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W4414439658