Ghady Haidar1,2, Will Garner2, Joshua A Hill3,4. 1. Department of Medicine, University of Pittsburgh School of Medicine. 2. Division of Infectious Diseases, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. 3. Department of Medicine, University of Washington. 4. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Abstract
PURPOSE OF REVIEW: Data on the infectious complications of anti-CD19 chimeric antigen receptor-modified T-cell (CAR-T-cell) therapies are scant. The approaches to preventing and managing infections among CAR-T-cell recipients are extrapolated from those of patients with other hematological malignancies. Understanding the incidence and risk factors of infections in these patients will improve clinical outcomes. RECENT FINDINGS: Infections occur in 23-42% of CAR-T-cell recipients and are most frequent in the first month after infusion, declining sharply thereafter. Risk factors include preinfusion (e.g., prior hematopoietic cell transplant, underlying malignancy) and postinfusion variables (e.g., cytokine release syndrome [CRS], neutropenia). Neutropenic fever after CAR-T-cell therapy is nearly universal but is confounded by CRS. The timeline of infections can be divided into preinfusion (because of the preparative regimen); 0-30 days after infusion, when bacterial infections predominate; and 30 days onwards, when respiratory viral infections predominate. Fungal and herpesviridae infections are uncommon. SUMMARY: Recent studies have shed light on the epidemiology of infections after CAR-T-cell therapy. Future efforts should focus on identifying modifiable risk factors for infection, defining neutropenic fever in the setting of CRS, determining the benefit of antimold prophylaxis, and identifying the optimal approach to viral monitoring, vaccination, and immunoglobulin replacement.
PURPOSE OF REVIEW: Data on the infectious complications of anti-CD19 chimeric antigen receptor-modified T-cell (CAR-T-cell) therapies are scant. The approaches to preventing and managing infections among CAR-T-cell recipients are extrapolated from those of patients with other hematological malignancies. Understanding the incidence and risk factors of infections in these patients will improve clinical outcomes. RECENT FINDINGS:Infections occur in 23-42% of CAR-T-cell recipients and are most frequent in the first month after infusion, declining sharply thereafter. Risk factors include preinfusion (e.g., prior hematopoietic cell transplant, underlying malignancy) and postinfusion variables (e.g., cytokine release syndrome [CRS], neutropenia). Neutropenic fever after CAR-T-cell therapy is nearly universal but is confounded by CRS. The timeline of infections can be divided into preinfusion (because of the preparative regimen); 0-30 days after infusion, when bacterial infections predominate; and 30 days onwards, when respiratory viral infections predominate. Fungal and herpesviridae infections are uncommon. SUMMARY: Recent studies have shed light on the epidemiology of infections after CAR-T-cell therapy. Future efforts should focus on identifying modifiable risk factors for infection, defining neutropenic fever in the setting of CRS, determining the benefit of antimold prophylaxis, and identifying the optimal approach to viral monitoring, vaccination, and immunoglobulin replacement.
Authors: Matthew K Hensley; William G Bain; Jana Jacobs; Sham Nambulli; Urvi Parikh; Anthony Cillo; Brittany Staines; Amy Heaps; Michele D Sobolewski; Linda J Rennick; Bernard J C Macatangay; Cynthia Klamar-Blain; Georgios D Kitsios; Barbara Methé; Ashwin Somasundaram; Tullia C Bruno; Carly Cardello; Feng Shan; Creg Workman; Prabir Ray; Anuradha Ray; Janet Lee; Rahil Sethi; William E Schwarzmann; Mark S Ladinsky; Pamela J Bjorkman; Dario A Vignali; W Paul Duprex; Mounzer E Agha; John W Mellors; Kevin D McCormick; Alison Morris; Ghady Haidar Journal: Clin Infect Dis Date: 2021-08-02 Impact factor: 9.079