Pattern of IgG Testing and Immunoglobulin-Replacement Therapy in Patients with Non-Hodgkin Lymphoma

Introduction: Patients with Non-Hodgkin Lymphoma (NHL) are at increased risk of secondary hypogammaglobulinemia (SHG), SHG-related infections as well as mortality. There are several factors that contribute to SHG among NHL patients; some related to the nature of the condition itself while others are driven by the immunosuppressive therapies used to treat NHL, such as anti-CD20 monoclonal antibodies or chimeric antigen receptor T-cell therapies (Jolles et. al. Front Oncol 2023). In this context, it is crucial that IgG levels are closely monitored in NHL patients, particularly those treated with immunosuppressive therapy. For NHL patients presenting with SHG and severe, recurrent or unusual infections, immunoglobulin-replacement therapy (IgRT) is recommended (Otani et. al. J Allergy Clin Immunol 2022). Although effectiveness of IgRT therapy among patients with SID has been previously assessed , there is a need to better characterize the treatment journey regarding IgG testing, IgRT initiation, and its use over time. Herein, we present the results from a retrospective cohort study assessing the frequency and timing of IgG level assessment and patterns of IgRT use among NHL patients with recurrent or severe infections. Methods: This retrospective, real-world evidence study utilized adjudicated claims data from PharMetrics Plus, a database of insured US patients. Patients ICD-diagnosed with NHL (ICD-10 C82, C83, C84, C85) between Jan-2015 and Sep-2023, with one severe infection or 2 non-severe infections over 12 months were included. Index date was defined as first severe infection or the second of two non-severe infections after NHL diagnosis. Patients were included if they had a minimum of 12-month continuous insurance enrolment pre-index and 6-month post-index. Patients who received IgRT between NHL diagnosis and index or with a diagnosis of primary immunodeficiency or any other condition that could have led to IgRT, or IgG use for immunomodulation, were excluded. Index demographic and clinical characteristics, frequency of IgG testing, time from NHL diagnosis to IgG testing, time to IgRT therapy, IgRT frequency and duration were evaluated. Analyses were stratified based on IgRT use post-index (IgRT users and non-IgRT users). Results: Overall, 47,623 NHL patients were included in the analytic cohort. IgRT was prescribed to only 651 (1.4%) patients. Mean (SD) age [56.2 (16.0) vs 57.1 (15.8)] and sex distribution (50.7% vs 50.3% of males) were comparable between IgRT and non-IgRT users. Pre-index antibiotic use [155 (23.8%) vs 8,150 (17.3%)] and neutropenia [184 (28.3%) vs 5,242 (11.2%)] were more common among IgRT users. IgG levels were only assessed in 198 (30.4%) and 6,663 (14.2%) of IgRT and non-IgRT users, respectively. Mean (SD) time to first IgG test was 17.1 (18.6) months for IgRT users and 13.8 (19.2) months for non-IgRT users. The rate of tests per person-year was 2.5 for IgRT users and 1.2 for non-IgRT users. Mean (SD) times from NHL diagnosis and from index to first IgRT use were 31.5 (22.4) and 20.6 (19.5) months, respectively. Mean (SD) total number of IgRT doses was 2.7 (1.6), 4.1 (2.6) and 6.8 (5.3) at 3-, 6- and 12-month after start date of IgRT. Mean (SD) weeks between IgRT doses was 6.8 (4.1), 10.8 (8.7) and 17.2 (17.1), respectively. Conclusions: Our study illustrates that most NHL patients with prior severe or recurrent infections do not get IgG levels assessed. IgRT use is low, and among patients who receive IgRT, total number of doses and frequency seem to be heterogeneous and suboptimal. As new immunosuppressive therapies are developed, consensus on timing of IgG level measurement and IgRT treatment is warranted to prevent life-threatening infections in NHL patients presenting with SHG.