While more than half of non-Hodgkin lymphomas (NHL) can be cured with modern frontline chemoimmunotherapy regimens, outcomes of relapsed and/or refractory (r/r) disease in subsequent lines remain poor, particularly if considered ineligible for hematopoietic stem cell transplantation. Hence, r/r NHLs represent a population with a high unmet medical need. This therapeutic gap has been partially filled by adoptive immunotherapy. CD19-directed autologous chimeric antigen receptor (auto-CAR) T cells have been transformative in the treatment of patients with r/r B cell malignancies. Remarkable response rates and prolonged remissions have been achieved in this setting, leading to regulatory approval from the U.S. Food and Drug Administration (FDA) of four CAR T cell products between 2017 and 2021. This unprecedented success has created considerable enthusiasm worldwide, and autologous CAR T cells are now being moved into earlier lines of therapy in large B cell lymphoma. Herein, we summarize the current practice and the latest progress of CD19 auto-CAR T cell therapy and the management of specific toxicities and discuss the place of allogeneic CAR T development in this setting.
Keywords: cellular therapy; chimeric antigen receptor; lymphoma.