Association of CD19-targeted Chimeric Antigen Receptor (CAR) T-cell Therapy with Hypogammaglobulinemia, Infection, and Mortality

Overview

Journal J Allergy Clin Immunol

Specialty Allergy & Immunology

Date 2024 Nov 6

PMID 39505278

Authors

Natalia M Sutherland

Baijun Zhou

Lingxiao Zhang

Mei-Sing Ong

Joseph S Hong

Andrew Pak

Katherine J Liu

Matthew J Frigault

Marcela V Maus

Joshua A Hill

Kerry Reynolds

Jolan E Walter

Carlos A Camargo Jr

Sara Barmettler

Affiliations

Soon will be listed here.

Abstract

Background: CD19-targeted chimeric antigen receptor T-cell therapy (CAR-T therapy) has revolutionized the treatment of hematologic malignancies. As these cells target CD19 receptors on B cells, there is the potential for B-cell aplasia and hypogammaglobulinemia. Data on the degree and clinical significance of hypogammaglobulinemia are sparse.

Objectives: We sought to evaluate hypogammaglobulinemia after CD19-targeted CAR-T therapy and risk factors for hypogammaglobulinemia, infections, and mortality.

Methods: We performed a retrospective evaluation of 579 patients receiving CD19-directed CAR-T therapy and evaluated demographics, hypogammaglobulinemia (IgG ≤600 mg/dL), infections prior to and after CAR-T therapy, and risk factors for hypogammaglobulinemia, infection, hospitalizations, and mortality.

Results: Patients had a mean age of 64 years and 64% were male. Prior to CAR-T therapy, 60% of patients had hypogammaglobulinemia, which increased to 91% post-CAR-T therapy. Mean IgG levels decreased from pre- to post-CAR-T therapy levels (587 to 362 mg/dL; P < .0001). Thirty-seven percent of patients developed a serious infection post-CAR-T therapy. Hypogammaglobulinemia prior to CAR-T therapy was associated with worsening hypogammaglobulinemia after CAR-T therapy. Hypogammaglobulinemia post CAR-T therapy was associated with an increased risk of serious infection following CAR-T therapy (incidence rate ratio: 2.7; 95% CI: 1.5-5.2; P = .002). Risk factors for mortality included mild hypogammaglobulinemia (400 mg/dL < IgG ≤ 600 mg/dL), infections ≤100 days post-CAR-T therapy, and hospitalizations for infections. Immunoglobulin replacement was associated with a decreased risk of mortality.

Conclusions: We identified ∼90% of patients with hypogammaglobulinemia after CAR-T therapy. Hypogammaglobulinemia before CAR-T therapy was strongly predictive of worsening hypogammaglobulinemia after CAR-T therapy, which was associated with an increased risk of serious infection and mortality post CAR-T therapy. Increased immunological monitoring is needed to identify high-risk patients who may benefit from interventions to decrease morbidity and mortality.

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