Combining CAR T-Cell Therapy and Nivolumab to Overcome Immune Resistance in THRLBCL: A Case Report
Por:
Munarriz, D, López-Godino, O, Martinez-Cibrian, N, Albiol, N, Brillembourg, H, Navarro-Velázquez, S, Español-Rego, M, Casanueva, S, García-Tomás, L, Muñoz-Sanchez, G, Alserawan, L, Benitez-Ribas, D, Magnano, L, Correa, JG, Rivero, A, Mozas, P, Gine, E, Rodríguez-Lobato, LG, Martínez-Roca, A, Montoro-Lorite, M, Ayora, P, Esteve, J, Frutos, L, Balagué-Ponz, O, Urbano-Ispizua, A, González-Navarro, EA, Juan-Otero M, Delgado, J and Ortiz-Maldonado, V
Publicada:
23 sep 2025
Resumen:
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.
Filiaciones:
Munarriz, D:
Hosp Clin Barcelona, Dept Hematol, Barcelona 08036, Spain
López-Godino, O:
Hosp Univ Morales Meseguer, Ctr Reg Hemodonac, Dept Hematol, IMIB Pascual Parrilla, Murcia 30008, Spain
Martinez-Cibrian, N:
Hosp Clin Barcelona, Dept Hematol, Barcelona 08036, Spain
Univ Barcelona, Fac Med, Barcelona 08007, Spain
Albiol, N:
Hosp Clin Barcelona, Dept Hematol, Barcelona 08036, Spain
Univ Barcelona, Fac Med, Barcelona 08007, Spain
Brillembourg, H:
Hosp Clin Barcelona, Dept Hematol, Barcelona 08036, Spain
Navarro-Velázquez, S:
Univ Barcelona, Fac Med, Barcelona 08007, Spain
Hosp Clin Barcelona, Dept Immunol, Barcelona 08036, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain
Español-Rego, M:
Hosp Clin Barcelona, Dept Immunol, Barcelona 08036, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain
Casanueva, S:
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain
García-Tomás, L:
Hosp Univ Morales Meseguer, Ctr Reg Hemodonac, Dept Hematol, IMIB Pascual Parrilla, Murcia 30008, Spain
Muñoz-Sanchez, G:
Hosp Clin Barcelona, Dept Immunol, Barcelona 08036, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain
Alserawan, L:
Hosp Clin Barcelona, Dept Immunol, Barcelona 08036, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain
Benitez-Ribas, D:
Hosp Clin Barcelona, Dept Immunol, Barcelona 08036, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain
Magnano, L:
Hosp Clin Barcelona, Dept Hematol, Barcelona 08036, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain
Correa, JG:
Hosp Clin Barcelona, Dept Hematol, Barcelona 08036, Spain
Rivero, A:
Hosp Clin Barcelona, Dept Hematol, Barcelona 08036, Spain
Univ Barcelona, Fac Med, Barcelona 08007, Spain
Mozas, P:
Hosp Clin Barcelona, Dept Hematol, Barcelona 08036, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain
Gine, E:
Hosp Clin Barcelona, Dept Hematol, Barcelona 08036, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain
Rodríguez-Lobato, LG:
Hosp Clin Barcelona, Dept Hematol, Barcelona 08036, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain
Martínez-Roca, A:
Hosp Clin Barcelona, Dept Hematol, Barcelona 08036, Spain
Univ Barcelona, Fac Med, Barcelona 08007, Spain
Montoro-Lorite, M:
Hosp Clin Barcelona, Dept Hematol, Barcelona 08036, Spain
Ayora, P:
Hosp Clin Barcelona, Dept Hematol, Barcelona 08036, Spain
Esteve, J:
Hosp Clin Barcelona, Dept Hematol, Barcelona 08036, Spain
Univ Barcelona, Fac Med, Barcelona 08007, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain
Frutos, L:
Hosp CU Virgen Arrixaca, Dept Nucl Med, Murcia 30120, Spain
Balagué-Ponz, O:
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain
Hosp Clin Barcelona, Dept Pathol, Barcelona 08036, Spain
Urbano-Ispizua, A:
Hosp Clin Barcelona, Dept Hematol, Barcelona 08036, Spain
Univ Barcelona, Fac Med, Barcelona 08007, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain
Josep Carreras Res Inst, Barcelona 08916, Spain
González-Navarro, EA:
Hosp Clin Barcelona, Dept Immunol, Barcelona 08036, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain
Juan-Otero M:
Univ Barcelona, Fac Med, Barcelona 08007, Spain
Hosp Clin Barcelona, Dept Immunol, Barcelona 08036, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain
Clin St Joan Deu Immunotherapy Platform, Barcelona 08036, Spain
Delgado, J:
Hosp Clin Barcelona, Dept Hematol, Barcelona 08036, Spain
Univ Barcelona, Fac Med, Barcelona 08007, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain
Ortiz-Maldonado, V:
Hosp Clin Barcelona, Dept Hematol, Barcelona 08036, Spain
Univ Barcelona, Fac Med, Barcelona 08007, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain
Fred Hutchinson Canc Ctr, Clin Res Div, Seattle, WA 98109 USA
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