Treatment Patterns of Immunoglobulin Replacement Therapy Among Patients with Multiple Myeloma in the United States: A Real-World Analysis
Authors: Ida Fidelia , Ramakrishna Bharat , Nasserinejad Kaz , Radu Adriana , Lawo John-Philip , Zhang Xiang , Gardiner David , Yoon Lara , Shen John , Dabrowski Elizabeth C. , Khan Saarah , Espinoza Gabriela , Shahid Zainab , Giralt Sergio A. 
Published: December 2024

Background: Hypogammaglobulinemia (HGG), is defined as low levels (≤7 g/L) of functional serum immunoglobulin (Ig) G, with IgG levels of &lt;4 g/L often referred to as secondary immunodeficiency (SID). Patients (pts) with relapsed/refractory multiple myeloma (RRMM) are at risk of SID, which can be related to underlying disease or B-cell depleting therapy (e.g. due to CAR T, bispecific antibodies, alkylating agents, steroids, etc.). SID can be associated with increased infection, thus RRMM pts are at greater risk of frequent and severe infections. To mitigate infection risk, Ig replacement therapy (IgRT) can be used; however, guidelines for IgRT use vary widely.

Aims: This retrospective cohort study aimed to assess patterns of IgRT use following RRMM diagnosis in patients with RRMM across the United States (US).

Methods: This retrospective study used the US Optum Market Clarity database (data available 10/2015 to 9/2023), to assess outcomes in pts ≥18 years old with RRMM (defined by ICD-10 diagnosis codes C90.00 and C90.02). Patients were excluded if they had history of non-malignant conditions indicated for IgRT (including primary immunodeficiency) prior to MM diagnosis, or fewer than 6 months of baseline data pre-index, defined as date of incident or prevalent RRMM diagnosis. Variables of interest included baseline pt characteristics, cancer therapies, IgG levels, and patterns of IgRT use. The follow-up period began 1 day after RRMM diagnosis and ends at the earliest of: death, end of observability, or end of study period.

Results: A total of 43,793 pts were included in the study. In the baseline 6-month data period, the mean (standard deviation [SD]) age of the study population was 66.4 (12.0), 44.6% (n=19,533) of pts were male (40.5%, n=17,725 female, 14.9% n=6,535 unknown), and 57.1% (n=25,001) of pts were Caucasian. Overall, 10.1% (n=4,409) had history of other heme malignancies, 11.0% (n=4,819) had any grade of neutropenia, and 3.6% (n=1,588) had documented SID. A total of 20.1% (n=8,798) had evidence of baseline IgG lab results. Only 1.2% (n=516) of pts received IgRT, 8.4% (n=3,694) received prophylactic antibiotics and 30.8% (n=13,497) had been vaccinated.

During the follow-up period, cancer treatment use was as follows: immunomodulatory drugs: n=13,861, 31.7%, proteasome inhibitors: n=13,393, 30.6%, steroids: n=10, 948, 25.0%, HSCT: n=8,229, 18.8%, alkylating agents: n=6,652, 15.2%, CD38 antibodies: n=5,826, 13.3%, CD20 antibodies: n=897, 2.0%, CAR T: n=149, 0.3%, bispecific antibodies: n=61, 0.1%.

In the follow-up period, IgG lab results were available in 30.1% (n=13,183) of pts. First IgG level observed was ≥6 g/L in n=9,931 (75.3% of the 13,183), IgG 4-6 g/L in n=1,711 (13.0%) and IgG &lt;4 g/L in n= 1,541 (11.7%).

Overall, 4.1% (n=1,789) of the study population (n=43,793) were treated with IgRT post-RRMM diagnosis. In total, 2.8% (n=1,232) of patients received IVIG, 0.1% (n=30) received SCIG, and the route of IgRT administration was unknown for 1.2% (n=527). The median (interquartile range) time from RRMM diagnosis date to IgRT initiation was 276.0 (63.0, 712.5) days. In the follow-up period, 9,001 pts (20.6%) received prophylactic antibiotics, 17,775 (40.6%) had prophylactic antivirals and 23,609 (53.9%) had vaccinations.

Among 42,930 pts without IgRT prior to RRMM diagnosis, infections were experienced by 37.7% (n=16,200) of pts, with 14.3% (n=6,131) of pts experiencing serious bacterial infections in the follow-up period.

Conclusion: Despite a sizeable infection burden and treatment with cancer therapies known to cause SID/HGG,these real-world data reveal that patient use of IgRT post RRMM diagnosis is lower than what would be expected, based on guidelines, at just 4.1% despite the potential benefit of IgRT. This study suggests suboptimal IgG testing and IgRT use in this population, and the need to raise awareness of using IgRT to manage SID in patients with RRMM.