CAR T-cell therapy for B-cell lymphoma.

Chimeric antigen receptor-modified (CAR) T-cell therapy targeting CD19 has revolutionized the treatment of relapsed or refractory B-cell lymphomas. Based on unprecedented response rates and durability of response in high risk B-cell lymphoma patients, anti-CD19 CAR T-cell therapy was rapidly approved by the FDA for a variety of lymphoma subtypes. Anti-CD19 CAR T-cell therapy is now considered standard of care for patients with relapsed or refractory (R/R) aggressive non-Hodgkin's Lymphoma (NHL) after 2 or more lines of therapy. Three second-generation anti-CD19 CAR T-cell products have been FDA approved for R/R aggressive B-cell lymphoma and FDA approval has been obtained for Mantle Cell Lymphoma and Follicular lymphoma as well. This has ensured broad access to CAR T-cell therapy for patients with NHL and new real-world trials have helped confirm feasibility of CAR T-cell therapy for a broad patient population. The emergence of CAR T-cell therapy will likely provide a new patient population who is status post anti-CD19 CAR T-cell therapy. Investigation of mechanisms of failure of CAR T-cell therapy and clinical trials to study strategies to address this are thus required. Here we provide a thorough review on the use of the FDA approved anti-CD19 CAR T-cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel in patients with indolent or aggressive B-cell lymphoma, and touch on mechanisms of failure of CAR T-cell therapy and potential approaches which are currently under investigation to address this.