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Infectious complications of CAR T-cell therapy across novel antigen targets in the first 30 days.
Mikkilineni, Lekha; Yates, Bonnie; Steinberg, Seth M; Shahani, Shilpa A; Molina, John C; Palmore, Tara; Lee, Daniel W; Kaplan, Rosandra N; Mackall, Crystal L; Fry, Terry J; Gea-Banacloche, Juan; Jerussi, Theresa; Nussenblatt, Veronique; Kochenderfer, James N; Shah, Nirali N.
Afiliación
  • Mikkilineni L; Surgery Branch, National Cancer Institute.
  • Yates B; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute.
  • Steinberg SM; Biostatistics and Data Management Section, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, and.
  • Shahani SA; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute.
  • Molina JC; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute.
  • Palmore T; Laboratory of Clinical Immunology and Microbiology Infectious Disease, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
  • Lee DW; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute.
  • Kaplan RN; Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Virginia, Charlottesville, VA.
  • Mackall CL; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute.
  • Fry TJ; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute.
  • Gea-Banacloche J; Department of Pediatrics, Stanford University, Stanford, CA.
  • Jerussi T; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute.
  • Nussenblatt V; University of Colorado Anschutz Medical Campus and Center for Cancer and Blood Disorders, Children's Hospital of Colorado, Aurora, CO.
  • Kochenderfer JN; Division of Clinical Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD; and.
  • Shah NN; National Institutes of Health Clinical Center, Bethesda, MD.
Blood Adv ; 5(23): 5312-5322, 2021 12 14.
Article en En | MEDLINE | ID: mdl-34619768
Infections are a known complication of chimeric antigen receptor (CAR) T-cell therapy with data largely emerging from CD19 CAR T-cell targeting. As CAR T-cell therapy continues to evolve, infection risks and management thereof will become increasingly important to optimize outcomes across the spectrum of antigens and disease targeted. We retrospectively characterized infectious complications occurring in 162 children and adults treated among 5 phase 1 CAR T-cell clinical trials. Trials included targeting of CD19, CD22, disialoganglioside (GD2) or B-cell maturation antigen (BCMA). Fifty-three patients (32.7%) had 76 infections between lymphocyte depleting (LD) chemotherapy and day 30 (D30); with the majority of infections (61, 80.3%) occurring between day 0 (D0) and D30. By trial, the highest proportion of infections was seen with CD22 CAR T cells (n = 23/53; 43.4%), followed by BCMA CAR T cells (n = 9/24; 37.5%). By disease, patients with multiple myeloma had the highest proportion of infections (9/24; 37.5%) followed by acute lymphoblastic leukemia (36/102; 35.3%). Grade 4 infections were rare (n = 4; 2.5%). Between D0 and D30, bacteremia and bacterial site infections were the most common infection type. In univariate analysis, increasing prior lines of therapy, recent infection within 100 days of LD chemotherapy, corticosteroid or tocilizumab use, and fever and neutropenia were associated with a higher risk of infection. In a multivariable analysis, only prior lines of therapy and recent infection were associated with higher risk of infection. In conclusion, we provide a broad overview of infection risk within the first 30 days post infusion across a host of multiple targets and diseases, elucidating both unique characteristics and commonalities highlighting aspects important to improving patient outcomes.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoterapia Adoptiva / Mieloma Múltiple Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Blood Adv Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoterapia Adoptiva / Mieloma Múltiple Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Blood Adv Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos