CAR-T Therapy, the End of a Chapter or the Beginning of a New One?

SIMPLE SUMMARY: CAR-T therapy is a breakthrough treatment in our fight against cancer. It was recently approved for the treatment of advanced diffuse large B-cell lymphoma and acute lymphoblastic leukaemia after the failure of previous multiple therapies. The positive results achieved in the registration studies for those patients were remarkable. Unfortunately, this was not the end of this chapter. Disease relapses occur in the range of 30–60% of patients treated with CAR-T therapy. Cytokine release syndrome represents a major side effect for treatment with CAR-T therapy. Notwithstanding, the high positive results triggered the start of a huge research activity of CAR-T therapy in other haematologic malignancies such as acute myelogenous leukaemia, Hodgkin’s disease, chronic lymphocytic leukaemia, and multiple myeloma. The research is also trying to overcome the hurdles stated above. These activities represent a new chapter in the management of haematologic malignancies with CAR-T therapy. ABSTRACT: Chimeric antigen receptor-T (CAR-T) therapy targeting CD19 has revolutionised the treatment of advanced acute lymphoblastic leukaemia (ALL) and diffuse large B-cell lymphoma (DLBCL). The ability to specifically target the cancer cells has shown high positive results as reported in the registration studies. The success of CAR-T therapy in the first two indications led to the initiation of a large number of studies testing CAR-T therapy in different haematologic tumours such as acute myelogenous leukaemia (AML), Hodgkin’s disease (HD), chronic lymphocytic leukaemia (CLL), multiple myeloma (MM), as well as different solid tumours. Unfortunately, relapses occurred in patients treated with CAR-T therapy, calling for the development of effective subsequent therapies. Likewise, this novel mechanism of action was also accompanied by a different toxicity profile, such as cytokine release syndrome (CRS). Patients’ access to the treatment is still limited by its cost. Notwithstanding, this did not prohibit further development of this new therapy to treat other malignancies. This research activity of CAR-T therapy moves it from being used as an end-stage treatment for ALL and DLBCL to a new therapeutic option for a wide range of patients with different haematologic and solid tumours.