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Correspondence to Dr Sarah Brem Sunshine, Ophthalmology and Visual Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA; [email protected]
Introduction
Chimeric antigen receptor T-cell (CAR T) therapy represents a significant advancement in adoptive cellular therapy for haematological malignancies. This novel treatment modality has shown great promise in the treatment of refractory haematological malignancies. As more patients have been treated with CAR T therapy, off-target toxicities have been identified including hepatic, neurological, cardiovascular, pulmonary and renal toxicities.1 2 The identification of ophthalmic toxicities is important for the optimal management of patients on CAR T therapy.
CAR Ts are genetically engineered T cells that express anti-CD19 CARs, which target CD19 positive tumour cells. These modified T-cells are transferred to patients as a new form of targeted immunotherapy and can be host-derived (autologous) or donor-derived (allogeneic), although at the time of writing, autologous CAR Ts are the only Food and Drug Administration (FDA) approved, standard of care, CAR T therapy for relapsed refractory large B-cell lymphoma (LBCL).3
Although CAR T therapy is potentially curative with objective response rates of 60%–80% with 5-year progression-free survival of 31%, the toxicities can be devastating if not recognised in a timely manner.4 CAR T therapy can elicit significant and potentially life-threatening toxicities, including cytokine release syndrome (CRS) and neurological toxicity. These toxicities are due to an extensive systemic inflammatory syndrome, which can cause widespread inflammation resulting in failure of multiple organ systems.5 6 Neurotoxicity, otherwise termed immune effector cell-associated neurotoxicity syndrome (ICANS), is the most common adverse event reported in the literature.7 Due to the association of ICANS with increased intracranial pressure, the most common ophthalmological consultation for these patients has been to evaluate for evidence of papilloedema in the setting of cerebral oedema.8
CRS is caused by a lack of homeostasis in the physiological function of pro-inflammatory and anti-inflammatory cytokines due to disruption of the normal immune system. Studies report the incidence of CRS in CAR T therapy patients is approximately 10%–40% with a median time to onset of 2 days (range 1–12 days).9 10 CRS is characterised by constitutional symptoms including fevers, chills and hypotension. However, it can affect any organ system including respiratory, integumentary, gastrointestinal, and nervous systems.
While many systemic...