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Subcutaneous Immunoglobulin Replacement Following CD19-Specific Chimeric Antigen Receptor-T Cell Therapy for B-Cell Acute Lymphoblastic Leukemia

Year: 2018

Type: article

Abstract: Background: Chimeric antigen receptor-modified T cell therapy targeting CD19 (CART-19) has recently been approved for relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). Successful CART-19 therapy is expected to result in prolonged B cell aplasia and agammaglobulinemia. As such, immunoglobulin replacement is essential for the prevention of serious bacterial infections. Several studies in patients with primary humoral immunodeficiency, particularly agammaglobulinemia, have demonstrated decreased risk of bacterial infection with increasing IgG trough levels up to 1000 mg/dL. Subcutaneous immunoglobulin (SCIg) replacement is generally associated with more stable IgG levels and increased ease of administration. Methods: Retrospective chart review of 28 patients (median age 9.5 yrs, range 3-23 yrs) who received CART-19 for B-ALL at Children's Hospital of Philadelphia between April 2012 and December 2016 and currently on SCIg replacement. Median follow-up of 30 mos (range 9-65 mos) from CART-19 and 14.5 mos (range 5-59 mos) on SCIg.Table 1SCIg Dose and IgG Levels Expressed as Median (Range)Starting dose (mg/kg/wk)IgG level at 2 mos(mg/dL)IgG level (mg/dL)SCIg dose (mg/kg/wk)Infection-freeSinusitisPneumoniaIgG level<1000 mg/dLIgG level >1000 mg/dL1209781014.5867812.5117.5130(100-185)(685-1321)(685-1430)(578-1280)(595-847)(100-185)(100-175) Open table in a new tab Results: No patients were on routine immunoglobulin replacement at time of CART-19 therapy. All patients were started on intravenous immunoglobulin (IVIG) at 400 mg/kg monthly within 30 days of T cell infusion. Median IgG trough on IVIG was 595.5 mg/dL (range 378-1170 mg/dL). Patients were transitioned to SCIg at a median of 11.5 mos (range 4-20 mos). Twenty-seven/28 patients were started on 20% SCIg every 1-2 weeks, and one patient was started on 10% SCIg monthly. Doses were adjusted per home institution standards. Thirteen/28 patients developed sinusitis, and 4/28 patients developed chest x-ray confirmed pneumonia while on SCIg replacement. One of the patients with pneumonia had concurrent influenza A infection and required hospitalization for dehydration. The median IgG level during infection-free periods was significantly higher than the median IgG level at time of sinus infections (P-value .0498) and pneumonia (P-value .0116). IgG level did not correlate with SCIg dose in our patient cohort. Conclusion: SCIg may be used successfully in patients following CART-19 therapy. An IgG level >1000 mg/dL is associated with decreased risk of sinopulmonary infections. There was no correlation between SCIg dose and IgG level in our patient cohort, which may reflect individual differences in absorption and immunoglobulin metabolism. As such, we recommend routine monitoring of IgG levels with goal >1000 mg/dL to ensure optimal protection.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2017.12.103

Authors: Danielle E. Arnold, Colleen A. Callahan, Shannon L. Maude, Stephan A. Grupp, Jennifer Heimall

Institution: Children's Hospital of Philadelphia

Language: English

Topic: Immunodeficiency and Autoimmune Disorders

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,650