[CAR T-cell therapy for malignant B-cell lymphoma : A new treatment paradigm]

Following the first demonstration of efficacy of anti-CD19-directed chimeric antigen receptor (CAR) T cells in a patient with relapsed chronic lymphocytic leukemia (CLL) in 2011, pivotal studies for this innovative therapy were initially conducted in multiple relapsed or refractory (r/r) childhood and young adult acute B‑cell leukemia and in aggressive adult B‑cell lymphoma. The studies demonstrated efficacy even in chemotherapy-refractory disease, resulting in the first approval of autologous and genetically engineered T cells for the treatment of r/r B‑cell acute lymphoblastic leukemia (B-ALL) in the US for the product tisagenlecleucel (Kymriah®, Novartis) back in 2018. Approval for the treatment of r/r aggressive B‑cell lymphoma followed shortly thereafter for tisagenlecleucel and axicabtagene ciloleucel (Yescarta, Kite/Gilead). This review focuses on the treatment of aggressive B‑cell lymphoma and other CD19 positive B‑cell lymphomas by summarizing the study results of clinically tested CAR T cells, discussing possible resistance mechanisms, and providing an outlook on ongoing studies with new target antigens for the treatment of B‑cell lymphomas.