Characteristics and risk factors of infections following CD28-based CD19 CAR-T cells

Dayagi, Talya Wittmann; Sherman, Gilad; Bielorai, Bella; Adam, Etai; Besser, Michal J.; Shimoni, Avichai; Nagler, Arnon; Toren, Amos; Jacoby, Elad; Avigdor, Abraham

doi:10.1080/10428194.2021.1881506

Cited by 34 publications

(46 citation statements)

References 25 publications

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“…In one study, 22/36 (61%) of early infections (within first 30 days post-CAR T-cell infusion) were bacterial in origin. 36 This included common sites such as the bloodstream, genitourinary, lung and soft tissue; Clostridioides difficile infection was also seen ( Table 2 ). Indeed, there appears to be a high rate of C. difficile infection among this group with cohort infection rates ranging from 12.5% to 20%.…”

Section: Bacterial Infectionsmentioning

confidence: 99%

“…Indeed, there appears to be a high rate of C. difficile infection among this group with cohort infection rates ranging from 12.5% to 20%. 22 , 30 , 35 – 37 Bacterial infection occurred infrequently after 30 days. In another study, bacterial infection occurred in 17% of patients within the first 28 days after infusion: half of these infection episodes were bloodstream infections including a small minority from multidrug-resistant Gram-negative pathogens.…”

Section: Bacterial Infectionsmentioning

confidence: 99%

“…In one study only 2/88 (2.3%) patients experienced this (viraemia and pneumonitis, respectively). 36 Recently there was a case of prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a patient who had received CAR T-cell therapy targeting the BCMA. 43 , 44 Despite receiving convalescent plasma and the antiviral remdesivir, the patient had persistently elevated viral RNA throughout illness for more than 2 months before succumbing to the infection.…”

Section: Viral Infectionsmentioning

confidence: 99%

“… 22 Another cohort of 85 adult and paediatric patients documented only one fungal infection that occurred between 30 days and 60 days post-therapy. 36 Late invasive fungal infection typically occurred in patients who had persistent risk factors including neutropaenia and corticosteroid use. Of 40 patients with R/R DLBCL who received CAR T-cell therapy and were followed up for 1 year, only two fungal infections were reported.…”

Section: Fungal Infectionsmentioning

confidence: 99%

“… 51 – 53 Similarly, it has been strongly advocated that trimethoprim-sulfamethoxazole be used for PJP prophylaxis for a similar time period. 36 Some institutions provide PJP and VZV prophylaxis for a minimum of 6 months or until recovery of the CD4 count to over 200 cells/mm 3 . 35 The level of CD4 suppression after CAR T-cell therapy may require prolonged or alternative prophylaxis strategies (e.g.…”

Section: Infection Prevention Strategiesmentioning

confidence: 99%

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

Stewart

Henden

2021

Therapeutic Advances in Infection

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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.

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Section: Bacterial Infectionsmentioning

confidence: 99%

Section: Bacterial Infectionsmentioning

confidence: 99%

Section: Viral Infectionsmentioning

confidence: 99%

Section: Fungal Infectionsmentioning

confidence: 99%

Section: Infection Prevention Strategiesmentioning

confidence: 99%

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

Stewart

Henden

2021

Therapeutic Advances in Infection

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CAR‐T cell therapy

Franklin,

Pophali,

Jackson

et al. 2024

Molecular Hematology

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Improving the safety of CAR‐T‐cell therapy: The risk and prevention of viral infection for patients with relapsed or refractory B‐cell lymphoma undergoing CAR‐T‐cell therapy

Qian,

Yang,

Zhang

et al. 2024

American J Hematol

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Chimeric antigen receptor (CAR) T‐cell therapy, an innovative immunotherapeutic against relapsed/refractory B‐cell lymphoma, faces challenges due to frequent viral infections. Despite this, a comprehensive review addressing risk assessment, surveillance, and treatment management is notably absent. This review elucidates immune response compromises during viral infections in CAR‐T recipients, collates susceptibility risk factors, and deliberates on preventive strategies. In the post‐pandemic era, marked by the Omicron variant, new and severe threats to CAR‐T therapy emerge, necessitating exploration of preventive and treatment measures for COVID‐19. Overall, the review provides recommendations for viral infection prophylaxis and management, enhancing CAR‐T product safety and recipient survival.

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Characteristics and risk factors of infections following CD28-based CD19 CAR-T cells

Cited by 34 publications

References 25 publications

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

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

CAR‐T cell therapy

Improving the safety of CAR‐T‐cell therapy: The risk and prevention of viral infection for patients with relapsed or refractory B‐cell lymphoma undergoing CAR‐T‐cell therapy

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