Disparities in Monoclonal Immunoglobulin-Associated Disorders in a Large and Diverse Cohort from a US Tertiary Safety-Net Center
Authors: Aijaz Ali , Szalat Raphael E. 
Published: December 2024

Background:
The presence of monoclonal immunoglobulin (MIg) in serum or urine is commonly encountered in clinical practice and is notably more prevalent in the Black population. Most of the time, the MIg is a monoclonal gammopathy of undetermined significance (MGUS). However, it can also indicate the presence of an underlying disorder including multiple myeloma (MM), lymphoid proliferation, or a monoclonal gammopathy of clinical significance (MGCS). This study aimed to evaluate the demographics of MIg and its associated disorders within a large, diverse, and often underrepresented population from the largest safety-net hospital in New England.
Methods:
We conducted a retrospective review of electronic medical records (EMR) of patients evaluated at the Boston Medical Center between 2012 and 2022. We first used ICD-10 codes for MGUS, MIg, MM, AL amyloidosis, smoldering myeloma, and the MGCS diagnoses as previously described (Blood. 2018 Oct 4;132(14):1478-1485) to extract demographics and biologics data. A manual review was performed to validate these data. The 2014 IMWG criteria were used to define the different types of underlying plasma cell disorders. Patients without detected MIg in the serum or without data were excluded. Statistical comparisons were performed using the χ² test. This study was approved by the Boston University Institutional Review Board, and all patients provided written consent as per the Declaration of Helsinki. To reduce bias, AL amyloidosis patients referred from outside of Massachusetts were excluded.
Results:
Out of 2604 patients identified from our primary data extraction, 1131 patients were confirmed to have a monoclonal gammopathy in the serum. Of these, 497 patients (43.9%) were female, 343 patients were White (30.3%), 559 patients were Black (49.4%), 77 patients were non-Black Hispanic/Latino (6.8%), and 37 patients were Asian/Native Hawaiian/Pacific Islander/Middle Eastern (3.3%). There were an additional 115 patients whose race was unknown or unavailable.
IgG and IgA were the most frequent MIg isotype observed in 62% and 16% of the cohort, respectively. IgM, free light chain, and biclonal/oligoclonal gammopathies were present in 12%, 7.3%, and 2.7% of the cohort, respectively. 2 patients had monoclonal IgD gammopathy. The distribution of the MIg isotype varied across races and ethnicities with IgM isotype being significantly less frequent in Black compared to White patients (3.9% vs 24.5%, p &lt; 0.0001), and monoclonal FLC only being more frequent in Asian vs White patients (16.2% vs 6.4%, p = 0.0302).
In the entire cohort, the prevalence of MIg-associated conditions was as follows: MGUS in 663 of 1,131 patients (58.6%), MM in 272 of 1,131 patients (24.0%), smoldering myeloma in 50 of 1,131 patients (4.4%), B-cell lymphoproliferative disorders in 52 patients (4.6%), including 18 cases of Waldenström's macroglobulinemia (1.6%), AL amyloidosis in 48 of 1,131 patients (4.2%), and MGCS in 46 of 1,131 patients (4.1%). Compared to White patients, Black patients had higher prevalence of MGUS (60.6% vs 49.6%, p = 0.0012) and MM (27.9% vs 21.0%, p = 0.0203) but significantly lower prevalence of lymphoid proliferation (1.8% vs 9.6%, p &lt; 0.0001), AL Amyloidosis (2.0% vs 8.2%, p &lt; 0.0001), and MGCS (2.1% vs 6.7%, p = 0.0006).
Conclusion:
Although this retrospective study is subject to biases related to access to care and screening practices, as well as exclusion of patients with MGCS lacking circulating MIg, our findings indicate distinct distributions of MIg isotypes and associated disorders among different racial and ethnic groups. This suggests potentially distinct underlying biological processes in the development of plasma cell and lymphoid disorders, including MGCS. Further research is needed to confirm these findings and refine screening guidelines and management strategies for monoclonal gammopathy-associated disorders.