CAR-T - and a side order of IgG, to go? - Immunoglobulin replacement in patients receiving CAR-T cell therapy

Blood Rev. 2019 Nov:38:100596. doi: 10.1016/j.blre.2019.100596. Epub 2019 Aug 7.

Abstract

The development and regulatory approval of chimeric antigen receptor T cell (CAR-T) therapies targeting the B-lineage surface antigen CD19 represents a major milestone in cancer immunotherapy. This treatment also results in depletion of normal CD19+ B cells and is associated with hypogammaglobulinemia. These on-target, off-tumor toxicities may result in an increased risk for infection, particularly for encapsulated bacteria. Data regarding the efficacy and cost-effectiveness of prophylactic IgG replacement in CD19-targeted CAR-T cell therapy recipients is lacking, and current expert recommendations are extrapolated from the data for individuals with primary immune deficiencies. This article reviews CAR-T cell therapies targeting B-lineage lymphocytes, associated side effects, and considerations for the approach to management of hypogamaglobulinemia in this patient population. Studies are needed to establish evidence-based approaches to prophylactic immunoglobulin administration in this context, and strategies may differ by patient and CAR-T cell product characteristics.

Keywords: CAR; CD19; IVIG; IgG; Immunoglobulin; Infection; Prophylaxis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Agammaglobulinemia / etiology*
  • Agammaglobulinemia / pathology
  • Agammaglobulinemia / therapy*
  • Antigens, CD19 / analysis
  • B-Lymphocytes / pathology
  • Disease Management
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Immunotherapy, Adoptive / adverse effects*
  • Immunotherapy, Adoptive / methods
  • Neoplasms / complications
  • Neoplasms / pathology
  • Neoplasms / therapy*

Substances

  • Antigens, CD19
  • Immunoglobulin G