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

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

Joshua A Hill  1 , Sergio Giralt  2 , Troy R Torgerson  3 , Hillard M Lazarus  4
Affiliations
Review

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

Joshua A Hill et al. Blood Rev. 2019 Nov.

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.

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Figures

Figure 1.
Figure 1.. Algorithm for determining need to initiate IgG replacement therapy in the first 3 months after receiving anti-CD19 CAR-T cell therapy.
Beyond the first 3 months after CAR-T cell infusion, we recommend IgG supplementation in patients with IgG ≤400 mg/dL AND serious, persistent, or recurrent bacterial infections.
Figure 2.
Figure 2.. Serum IgG concentrations over time by intravenous versus subcutaneous routes of administration.
A) Serum IgG concentrations in a patient with X-linked agammaglobulinemia who received a single infusion of ~400 mg/kg of 5% IVIG. The horizontal line shows the average concentration. Adapted from Berger et al, Clin Immunol (2004) 112(1):1-7. B) Serum IgG concentration of the same patient in panel A while receiving ~160 mg/kg of 16% IgG subcutaneously every 7 days. Adapted from Berger et al, Clin Immunol (2004) 112(1):1-7. C) Mean serum IgG levels (+/− the standard deviation of median individual levels) in 18 previously untreated patients with primary immunodeficiencies given 100 mg/kg subcutaneous IgG for 5 days (days 1-5) followed by 100 mg/kg/week. 7 patients had IgG >500 mg/dL by day 7. Adapted from Borte et al, J Clin Immunol (2011) 31:952-961.
Fig 3.
Fig 3.
Algorithm for evaluating continuing need for IgG replacement.
See this image and copyright information in PMC

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