Chimeric Antigen Receptor T Cells in Hematologic Malignancies. Issue 3 (22nd February 2017) - Shank, Brandon R.
Abstract : Patients with B‐cell hematologic malignancies who progress through first‐ or second‐line chemotherapy have a poor prognosis. Early clinical trials with autologous anti‐CD19 chimeric antigen receptor (CAR) T cells have demonstrated promising results for patients who have relapsed or refractory disease. Lymphodepleting conditioning regimens, including cyclophosphamide, fludarabine, pentostatin, bendamustine, interleukin‐2, and total body irradiation, are often administered before the infusion of CAR T cells, allowing for greater T‐cell expansion. The major toxicity associated with CAR T‐cell infusions is cytokine release syndrome (CRS), a potentially life‐threatening systemic inflammatory disorder. The quick onset and progression of CRS require rapid detection and intervention to reduce treatment‐related mortality. Management with tocilizumab can help ameliorate the symptoms of severe CRS, allowing steroids, which diminish the expansion and persistence of CAR T cells, to be reserved for tocilizumab‐refractory patients. Other toxicities of CAR T‐cell therapy include neutropenia and/or febrile neutropenia, infection, tumor lysis syndrome, neurotoxicity and nausea/vomiting. A review of patients' medications is imperative to eliminate medications that may contribute to treatment‐related toxicities. Studies are ongoing to help optimize patient selection, preparation, safety, and management of individuals receiving CAR T cells. Long‐term follow‐up will help establish the place of CAR T cells in therapy.