4, 5, 7-11, 13-16, 35-40 Neurologic toxicities due to CAR T-cell therapy may occur concurrently with CRS or occur in the absence of CRS. 10-13, 34 The most prominent and well-described toxicity of CAR T cells is cytokine release syndrome (CRS), a constellation of symptoms including fever and hypotension that is caused by cytokines released by the infused T cells. 32, 33 Acute anaphylaxis and tumor lysis syndrome (TLS) have occurred following infusion of CAR T cells. 8, 16, 31 CAR T cells may damage normal tissues by unexpectedly cross-reacting with a protein that is not expressed on tumor cells. If the tumor-associated antigen to which the CAR is targeted is expressed on normal tissues, those tissues may be damaged, as is the case with normal B cells being depleted by anti-CD19 CAR T cells. We present guidelines for treating patients experiencing CRS and other adverse events following CAR T-cell therapy.ĬAR T cells can cause toxicity by several mechanisms. This review describes the toxicities caused by CAR T cells and reviews the published approaches used to manage toxicities. Pharmacologic management is complicated by the risk of immunosuppressive therapy abrogating the antimalignancy activity of the CAR T cells. Corticosteroids should be reserved for neurologic toxicities and CRS not responsive to tocilizumab. Interleukin-6 receptor blockade with tocilizumab remains the mainstay pharmacologic therapy for CRS, though indications for administration vary among centers. Aggressive supportive care is necessary for all patients experiencing CAR T-cell toxicities, with early intervention for hypotension and treatment of concurrent infections being essential. Neurologic toxicity due to CAR T cells might in some cases have a different pathophysiology than CRS and requires different management. CRS is the most common type of toxicity caused by CAR T cells. Cytokine release syndrome (CRS), a systemic inflammatory response caused by cytokines released by infused CAR T cells can lead to widespread reversible organ dysfunction. CAR T cells can potentially damage normal tissues by specifically targeting a tumor-associated antigen that is also expressed on those tissues. Early case reports of unexpected organ damage and deaths following CAR T-cell therapy first highlighted the possible dangers of this new treatment. Yet the use of CAR T cells is limited by potentially severe toxicities. Chimeric antigen receptor (CAR) T cells can produce durable remissions in hematologic malignancies that are not responsive to standard therapies.
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