PATTERNS OF IMMUNOGLOBULIN G TESTING AND INFECTION OUTCOMES IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA RECEIVING IMMUNOGLOBULIN REPLACEMENT THERAPY

Abstract

Introduction: Infections lead to mortality in up to 50% of patients (pts) with chronic lymphocytic leukemia (CLL). Immunoglobulin G (IgG) testing detects hypogammaglobulinemia (HGG; <500 mg/dL), a secondary immunodeficiency and risk factor for severe infections (SI) in pts with CLL. We hypothesized that increased IgG testing is associated with improved identification of HGG and reduced risk of SI in CLL. Methods: This retrospective study used de-identified patient data (structured data only) from the Mass General Brigham Research Registry. Eligible adults with CLL (diagnosed post-2010) had ≥12 months of clinical data and ≥3 visits/year. IgG levels and rates of HGG and SI pre- and post-immunoglobulin replacement therapy (IgRT) were compared. A multivariable logistic regression model examined the association of SI with IgG testing, controlling for IgRT, HGG, treatment, age, and sex. Results: Of 2842 pts with CLL and median (IQR) follow-up of 4.2 (2.2, 6.8) years, 1352 (47.6%) underwent IgG testing; 464 (34.3%) had HGG; 179 (6.3%) received IgRT; and 75.2% were treatment-naive. IgRT use (median [IQR] administrations of 2.0 [1.0, 4.0]) increased IgG levels (502.0 mg/dL [397.0, 615.0] vs. 367.0 mg/dL [245.0, 454.0]) and reduced rates of HGG (38.0% vs. 80.3%, p < 0.0001) and SI (33.7% vs. 51.0%, P=0.003) in the 12 months post-IgRT. IgG testing and IgRT use were independently associated with a significantly lower SI risk (Table). Pts with ≥3 versus 1-2 IgG tests were more likely to be identified with HGG (51.5% [321/623] vs. 19.6% [143/729], p < 0.0001), and pts with HGG who had ≥3 IgG tests were more likely to receive IgRT (32.7% [105/321] vs. 13.3% [19/143], p < 0.0001). Conclusions: Increased IgG testing was independently associated with lower risk of SI. Greater HGG risk awareness and more standardized IgG testing might reduce SI in pts with CLL. Study/writing support funder: Takeda Pharmaceuticals USA, Inc. Keywords: chronic lymphocytic leukemia (CLL), immunotherapy, late effects in lymphoma survivors The research was funded by: Analysis Group, Inc. conducted this study in collaboration with Takeda Pharmaceuticals USA, Inc. Under the direction of the authors, medical writing services were provided by Oxford PharmaGenesis Inc., and were funded by Takeda Pharmaceuticals USA, Inc. Conflict of interest: J. D. Soumerai Consultant or advisory role: Abbvie, AstraZeneca, Beigene, Bristol Myers Squibb, Roche, Seattle Genetics, TG Therapeutics, and Verastem Research funding: Adaptive Biotechnologies, Beigene, BostonGene, Genentech/Roche, GlaxoSmithKline, Moderna, Takeda, and TG Therapeutics Z. Yousif Employment or leadership position: Takeda Pharmaceuticals USA, Inc. and the University of California, San Diego. T. Gift Employment or leadership position: Takeda Pharmaceuticals USA, Inc. Stock ownership: Takeda R. Desai Employment or leadership position: Analysis Group, Inc. Analysis Group, Inc. Research funding: Takeda Pharmaceuticals L. Huynh Employment or leadership position: Analysis Group, Inc Research funding: Takeda Pharmaceuticals M. S. Duh Employment or leadership position: Analysis Group, Inc Research funding: Takeda Pharmaceuticals M. E. Sanchirico Employment or leadership position: Takeda Pharmaceuticals USA, Inc. Stock ownership: Takeda