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Blood Adv. 2019 Nov 26;3(22):3590-3601. doi: 10.1182/bloodadvances.2019000717.

Durable preservation of antiviral antibodies after CD19-directed chimeric antigen receptor T-cell immunotherapy.

Blood advances

Joshua A Hill, Elizabeth M Krantz, Kevin A Hay, Sayan Dasgupta, Terry Stevens-Ayers, Rachel A Bender Ignacio, Merav Bar, Joyce Maalouf, Sindhu Cherian, Xueyan Chen, Greg Pepper, Stanley R Riddell, David G Maloney, Michael J Boeckh, Cameron J Turtle

Affiliations

  1. Department of Medicine, University of Washington, Seattle, WA.
  2. Vaccine and Infectious Disease Division.
  3. Clinical Research Division, and.
  4. Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, WA.
  5. Department of Medicine, University of British Columbia, Vancouver, BC, Canada; and.
  6. Department of Laboratory Medicine, University of Washington, Seattle, WA.

PMID: 31743392 PMCID: PMC6880890 DOI: 10.1182/bloodadvances.2019000717

Abstract

The long-term effects of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy (CD19-CARTx) for B-cell malignancies on humoral immunity are unclear. We examined antiviral humoral immunity in 39 adults with B-cell malignancies who achieved durable complete remission without additional therapy for >6 months after CD19-CARTx. Despite CD19+ B-cell aplasia in all patients, the incidence of viral infections occurring >90 days post-CD19-CARTx was low (0.91 infections per person-year). Because long-lived plasma cells are CD19- and should not be direct targets of CD19-targeted chimeric antigen receptor T cells, we tested the hypothesis that humoral immunity was preserved after CD19-CARTx based on linear mixed-effects models of changes in serum total immunoglobulin G (IgG) concentration, measles IgG concentration, and the number of viruses or viral epitopes to which serum IgG was directed (the "antivirome") using the novel VirScan assay. Samples were tested pre-CD19-CARTx and ∼1, 6, and 12 months post-CD19-CARTx. Although total IgG concentration was lower post-CD19-CARTx (mean change, -17.5%), measles IgG concentration was similar (mean change, 1.2%). Only 1 participant lost measles seroprotection post-CD19-CARTx but had undergone allogeneic hematopoietic cell transplantation before CD19-CARTx. The antivirome was also preserved, with mean absolute losses of 0.3 viruses and 6 viral epitopes detected between pre- and post-CD19-CARTx samples. Most participants gained IgG to ≥2 epitopes for ≥2 viruses, suggesting that humoral immunity to some viruses may be maintained or recover after successful CD19-CARTx. These findings may differ in children. Studies of immunoglobulin replacement and vaccination after CARTx are warranted.

© 2019 by The American Society of Hematology.

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