Infectious complications of CAR T-cell therapy: a clinical update

Abstract

Chimeric antigen receptor (CAR) T-cell therapy is a revolutionary treatment modality used to treat haematological malignancies. Lymphocytes are engineered to produce CARs directed towards tumour cell antigens. Clinical trials have demonstrated impressive malignancy-related outcomes. Unfortunately, numerous off-target effects can cause toxicity-related adverse events in this population, the main being cytokine release syndrome and immune effector cell neurotoxicity syndrome. This causes significant patient morbidity and poor outcomes. Patients who receive CAR T-cell therapy are also profoundly immunosuppressed and often cytopenic, which is caused by a multitude of patient- and treatment-related factors. Thus, infection-related complications are also common in this group. Indeed, up to one third of patients will suffer a serious bacterial infection in the first 30 days after therapy. Viral respiratory tract infection appears to be the most common during the late phase and can be severe; one patient has died of influenza A infection. Fungal infection and cytomegalovirus (CMV) reactivation appear to be uncommon. Although institutional guidelines on infection-prevention strategies are available, there is a dearth of evidence to support their approach. Future research needs to target important unanswered questions that remain in this patient population in order to improve their short- and long-term outcomes.

Effects of B-Cell Lymphoma on the Immune System and Immune Recovery after Treatment: The Paradigm of Targeted Therapy

“…CAR-T-cell-associated toxicities are related to severe, supraphysiologic cytokine production and massive in vivo T-cell expansion. However, the latest studies are verifying the efficacy and safety results of this therapy in larger cohorts of patients with indolent B-NHL [ 136 ]. In addition, we are waiting to understand how CAR-T cells may impact the immunological landscape of this disease alongside its beneficial effect on the tumor cells.…”

Infectious Complications Following Car-T Cell Therapy for B Cell Non-Hodgkin Lymphoma: A Single-Center Experience and Review of the Literature

“…Despite high-degree of immunosuppression and prolonged neutropenia, fungal infections have remained infrequent in patients undergoing CAR-T cell therapy. Depending on the study, the incidence of IFI has ranged between 1-15%, and most of these infections occur as breakthrough to antifungal prophylaxis 14 . In our series, two patients (3.9%) developed IFIs: one fatal case of disseminated candidemia due to uconazole-resistant Candida glabrata (breakthrough uconazole prophylaxis) and one case of invasive pulmonary aspergillosis.…”

A unique hub‐and‐spoke model to optimize patient management in lymphoma using novel CAR‐T cell therapy in Southeast and South Asia

“…Other post-infusion side effects in the 28 days after treatment can include infection due to immunosuppression, and cytopenia. 12 Depending on their health, patients may be discharged, returning to the care of the referring physician in their home country two to 3 weeks after infusion, or may remain in Singapore for a further two to 3 weeks. Regardless of their recuperation location, patients are followed-up at regular intervals, or arrangements for further appointments are made if necessary.…”

“…The early use of tocilizumab has been shown to be effective in controlling side effects post‐infusion 11 and some patients may also benefit from short‐term corticosteroid therapy. Other post‐infusion side effects in the 28 days after treatment can include infection due to immunosuppression, and cytopenia 12 . Depending on their health, patients may be discharged, returning to the care of the referring physician in their home country two to 3 weeks after infusion, or may remain in Singapore for a further two to 3 weeks.…”