Current combinatorial CAR T cell strategies with Bruton tyrosine kinase inhibitors and immune checkpoint inhibitors.

CD19-targeted chimeric antigen receptor (CAR) T cell therapy has shown high efficacy in patients with refractory B-cell malignancies such as non-Hodgkin lymphoma and acute lymphoblastic leukemia. Despite promising results, responses are not durable in most patients. In addition, patients receiving CD19 CAR T cell therapy are at risk of developing severe, potentially life-threatening, adverse events including cytokine release syndrome and immune effector-cell associated neurotoxicity syndrome. Many combinatorial approaches are currently being investigated to improve CAR T cell in vivo function, antitumor effects, and mitigate toxicities. In this review, we discuss the use of ibrutinib and immune checkpoint inhibitors in combination with CAR T cell therapy in patients with lymphoid B-cell malignancies.