Audit of immunoglobulin monitoring and hypogammaglobulinaemia after B cell targeted therapy in a paediatric cohort in a high immune disease prevalence Region

Abstract

Introduction: Secondary hypogammaglobulinaemia or antibody deficiency (SAD) is an under-recognised complication of B cell-targeted therapies (BCTTs) in both autoimmune diseases (AIDs) and haematological malignancy. In 2019, UK recommendations were published for SAD in patients receiving BCTT,1 while, in 2022, the American Academy of Allergy, Asthma, and Immunology (AAAAI) produced guidance.2 Both publications recommend baseline immunoglobulin (Ig) measurements, followed by at 6–12-monthly intervals. Aims: Our aims here were to (1) describe Ig monitoring in our paediatric cohort receiving BCTT; and (2) audit our practice as per the 2019 UK and 2022 AAAAI guidance. Materials and Methods: Pharmacy records were screened for AID and malignancy patients receiving BCTT at Sidra Medicine between 2016 and 2024. Patients were between 0 and 18 years of age at the time of starting BCTT. Frequency and results of Ig testing were extracted from electronic medical records. These findings were audited against monitoring guidance from the 2019 and 2022 publications. Hypogammaglobulinaemia was defined as IgG below the lower limit of age-related reference range (irrespective of IgA and IgM levels). Values of IgG and the prevalence of hypogammaglobulinaemia were recorded at baseline and during follow-up. Results and Discussion: 98 patients were identified and 92 included with a minimum of 6 months’ follow-up duration (Fig 1); • Pre-BCTT baseline IgG results were available in 82/92 patients (89.1%); • 19/82 patients (23.2%) had low IgG levels at baseline; • 73/92 patients (79.3%) had IgG testing post-BCTTs; • Range of IgG measurements per patient: 1–14 timepoints over median follow-up of 0–72 months.Baseline IgG tests were almost always performed as per the guidance (Table 1). Baseline IgG was low in 23.2% patients, confirming the importance of this timepoint. However, post-BCTT IgG monitoring followed the guidance less strictly. Only 79.3% of patients had IgG measured post-BCTT, with variation in monitoring between specialties. Adherence to guidance was relatively lower in patients seen under neurology and nephrology. One systemic lupus erythematous (SLE) patient developed persistent low IgG after a solitary BCTT cycle. Further testing revealed an underlying primary immune deficiency disorder/inborn error of immunity. Conclusion: Baseline IgG tests were almost always performed as per the guidance, illustrating close adherence by clinicians. Furthermore, baseline IgG was low in 23.2% of patients, showing the clinical importance of baseline measurements, otherwise, low IgG during follow-up might be incorrectly attributed to BCTT. However, IgG measurement post-BCTT did not follow the guidance as closely. Overall, only 79.3% of patients had IgG measured post-BCTT, with clear variation in monitoring between specialties: haematology/oncology and rheumatology showed closer adherence compared with neurology and nephrology. The importance of baseline testing and monitoring was demonstrated by unmasking of a primary immune deficiency disorder in an SLE patient after a solitary BCTT cycle.3 Recommendations: (1) Protocol-driven approach to standardise IgG collection timepoints and improve monitoring; (2) Automation of IgG monitoring by including IgG orders as part of combined pharmacy–pathology rituximab order set; (3) Clinical Immunology review if persistent antibody deficiency and/or recurrent/severe infections develop after BCTT.