Durable preservation of antiviral antibodies after CD19-directed chimeric antigen receptor T-cell immunotherapy
Open Access
- 19 November 2019
- journal article
- research article
- Published by American Society of Hematology in Blood Advances
- Vol. 3 (22), 3590-3601
- https://doi.org/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.This publication has 53 references indexed in Scilit:
- B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor–transduced T cellsBlood, 2012
- Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid LeukemiaThe New England Journal of Medicine, 2011
- Cost-minimization analysis of the direct costs of TPE and IVIg in the treatment of Guillain-Barré syndromeBMC Health Services Research, 2011
- Human peripheral blood B‐cell compartments: A crossroad in B‐cell trafficCytometry Part B: Clinical Cytometry, 2010
- Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global PerspectiveTransplantation and Cellular Therapy, 2009
- Immunoglobulin Prophylaxis in Hematopoietic Stem Cell Transplantation: Systematic Review and Meta-AnalysisJournal of Clinical Oncology, 2009
- Immunoglobulin prophylaxis in chronic lymphocytic leukemia and multiple myeloma: systematic review and meta-analysisLeukemia & Lymphoma, 2009
- Duration of Humoral Immunity to Common Viral and Vaccine AntigensThe New England Journal of Medicine, 2007
- The common coldThe Lancet, 2003
- CD19 Antigen in Leukemia and Lymphoma Diagnosis and ImmunotherapyLeukemia & Lymphoma, 1995