How I treat adverse effects of CAR-T cell therapy

Abstract

Chimeric antigenreceptor (CAR) T cell therapy has demonstrated efficacy in B cell malignancies, particularly for acute lymphoblastic leukaemia (ALL) and non‑Hodgkin lymphomas. However, this regimen is not harmless and, in some patients, can lead to a multi organ failure. For this reason, the knowledge and the early recognition and management of the side effects related to CAR-T cell therapy for the staff is mandatory. In this review, we have summarised the current recommendations for the identification, gradation and management of the cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, as well as infections, and related to CAR-T cell therapy.

Adoptive Cell Therapy in Hepatocellular Carcinoma: Biological Rationale and First Results in Early Phase Clinical Trials

“…Numerous developments are underway with the evaluation of novel tumor targets to treat new categories of diseases such as Hodgkin’s disease [ 38 ], myeloid malignancies [ 39 ] or solid tumors, strategies to overcome resistance, largely due to the loss of the targeted tumor antigen [ 40 ], strategies to mitigate side-effects associated with CAR-T cells administration such as the cytokine release syndrome (CRS) or immune effector cells associated neurological syndromes (ICANS) [ 41 , 42 , 43 ] improved and more complex CAR structures designed to counteract the immune suppressive environment that characterizes many tumor types, support in vivo persistence of CAR-T cells and recruit endogenous immune effectors [ 44 ]. In addition, CAR-technologies are now combined with gene editing as a substitute to retroviral or lentiviral vector transduction [ 45 ] with the use of allogeneic cells that hold the promise of off-the-shelf medicines [ 46 ] and the genetic engineering of other immune cell subsets such as natural killer (NK) cells [ 47 ], γ/δ T cells, or macrophages.…”

New Era of Immunotherapy in Pediatric Brain Tumors: Chimeric Antigen Receptor T-Cell Therapy

“…The symptoms of CRS could be as easy as isolated fever, or potentially life-threatening, such as refractory hypotension or consumptive coagulopathy [ 84 , 85 ]. The severity of symptoms usually correlates with tumor burdens [ 86 ], and can be graded from one to four, based on the presence of fever, hypotension, hypoxia, end organ dysfunction, and admission to intensive care units [ 87 , 88 ]. Those symptoms can happen on the first day of the infusion of CAR T cells or can be delayed up to 14 days after the initiation of the delivery of CAR T cells.…”

Toxicities of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma: An Overview of Experience From Clinical Trials, Pathophysiology, and Management Strategies

“…As CRS is a systemic immune reaction, all organ systems could be affected. Typical early signs of CRS include fever ≥38°C, flu like symptoms, arthralgia, myalgia, and fatigue, which are mainly caused by INF-g and TNF-a production by CAR T cells themselves (78,87). Additionally, hypoxia, hypotension, and end organ damages such as liver function abnormalities, coagulopathy, decompensated heart failure, cardiac injury, and arrhythmia have already been reported in severe CRS, and CRS could develop into a life-threatening situation (42,55).…”

“…ICU admission should be evaluated when the patients develop signs of ≥grade 2 CRS or any grade ICANS. The treating hematologist should also alert the referral neurologist, if the patients present neurological symptoms (87). Cytopenia following CAR T cell therapy can be managed using hematopoietic growth factors and transfusion of erythrocytes or thrombocytes.…”

“…ICANS is primarily managed with close monitoring and supportive care (87). The ICE score is a valuable tool to assess and monitor the patient's neurologic status, which should be evaluated at least four times a day after the CAR T cell infusion (95).…”