Main Author: Omar Mostafa
Hypogammaglobulinemia is an under-recognized complication of B-cell targeted therapies (BCTT) in both autoimmune diseases (AID) and malignancy. Hypogammaglobulinemia may be transient or persistent, and may be associated with increased infection risk. While in 2019 and 2021, guidance was published for hypogammaglobulinemia in patients receiving BCTT, the majority of the primary literature quoted in these guidance articles is based on adult studies. Here we describe immunoglobulin (Ig) monitoring in our pediatric cohort receiving BCTT. We audited our practice as per the 2019 and 2021 guidance.
We retrospectively screened for all patients, including both AID and malignancy, who had received BCTT at Sidra Medicine, the main pediatric tertiary center in Qatar, between 2016-2022. Patients were identified from an audit of Pharmacy records. The frequency of Ig testing and measurements were extracted from the electronic medical records. Frequency of hypogammaglobulinemia and the need for immunoglobulin replacement (IGRT) were noted. These findings were audited against the monitoring guidance in the 2019 and 2021 publications.
Fifty-seven patients were included in the study: nephrotic syndrome 28, SLE 12, other rheumatological diseases 6, neurological diseases 6, malignancy 5. Pre-BCTT Ig results were available in 49/57 patients (85.9%), of which 13/49 (26.5%) had low IgG levels. During follow-up, 3/13 patients remained low, 6/13 normalized, and 4/13 did not have Ig’s repeated. Overall 39/57 (68.4%) patients had Ig testing after BCTT. The range was between 1-10 Ig measurements per patient over a follow-up duration of 1-36 months. 16/39 (41%) patients developed low Ig’s, of which 2 were transient; one SLE patient developed low Ig’s after only a single BCTT cycle, subsequent investigations suggesting CVID. However no patients required initiation of IGRT.
Baseline Ig measurements were almost always performed per the guidance, and indeed baseline Ig’s were abnormal in 26.5% patients. This confirms the importance of the baseline timepoint, whereby low baseline levels could be disease-related or due to other medications. Otherwise low Ig’s during follow-up might be incorrectly attributed to BCTT. However monitoring of immunoglobulins was less strictly followed compared with the guidance, with 68.4% patients having immunoglobulins measured post-BCTT. The importance of monitoring is demonstrated by the unmasking of common variable immunodeficiency in an SLE patient after a solitary BCTT cycle. Development of hypogammaglobulinemia did not by itself require IGRT, in the absence of recurrent infections.