Previous studies have revealed disparities in the prevalence, management, and outcomes of multiple myeloma (MM) in the U.S. based on patients’ race, ethnicity, and socioeconomic status. A study published in Blood Cancer Journal identified similar disparities in a global setting by examining the effect of drug-related adverse events (AEs) on patient outcomes across geographic regions.
“There’s still much to learn about these drugs. While they are effective, it is important for clinicians to fully understand the disparities and potential toxic effects associated with their use. This knowledge will enable them to provide more informed and effective treatment for patients,” said corresponding author Majid Jaberi-Douraki, PhD, professor of mathematics and data science and an affiliated researcher with the Johnson Cancer Research Center at Kansas State University.
Researchers used the U.S. Food and Drug Administration (FDA) AE Reporting System to examine 395,538 cases of MM from 129 reporting countries between 2004 and 2022. Dr. Jaberi-Douraki and colleagues sought to assess potential differences in drug safety profiles by analyzing the association between the occurrence of AEs and disparities in geographic regions, ethnicity, and sex.
The dataset was divided into six regions: North America (NA), Europe (EU), Asia (AS), Africa (AF), Oceania (OC), and Latin America and the Caribbean (LA). Only drugs and regimens with at least 20 reported cases were included, and regimens were limited to those containing no more than four active substances. NA represented 82.9% of the AE data.
There were 22 different drug regimens among the top 10 regimens used across regions. In NA, regimens were less diverse, with the top 10 regimens accounting for 89.39% of MM treatments. In contrast, EU showed greater diversity, with the top 10 regimens making up 53.05% and no single drug exceeding 10% of total reports. Nevertheless, across five of the six regions, lenalidomide was the most frequently used monotherapy or combination therapy agent (66%).
A comparative analysis of the 95% confidence intervals (CI) of reporting odds ratios suggested that regional differences may increase susceptibility to specific AEs in patient populations. Increased susceptibility included vascular toxicities among men in NA (CI 1.23), cardiotoxicities among both male and female patients in EU (CI 1.74 and 1.32, respectively) and AS (CI 1.27 and 1.12, respectively), and neoplasms among males and females in OC (CI 8.10 and 8.03, respectively).
Overall, deaths decreased across all continents. NA experienced a consistent annual decline in death rate that resulted in the greatest difference of 44.9% (dropping from 50.4% in 2004 to 5.5% in 2021), AS showed a drop in the death rate to 27.1% in 2022, and EU reported the least change in death rate, remaining at a roughly 27% average. Similarly, NA showed a decline in the rates of hospitalization to a low of 17% in 2021, while EU and AS maintained a stable pattern of hospitalizations.
Conversely, findings showed large fluctuations in both hospitalization and death rates in AF, LA, and OC, “suggesting variations in not only clinical practices and therapies but in toxicity and side effects from region to region,” said senior author Shahzad Raza, MD, MM specialist at the Taussig Cancer Center at Cleveland Clinic in Ohio. Results may also be attributed to the limited number of reported cases in these regions.
Researchers cited underreporting bias as a limitation inherent to FDA datasets. Nevertheless, “this is the best available dataset on AEs,” Dr. Raza said. Dr. Jaberi-Douraki added, “The patterns tell us, despite all the underreporting bias, if your drug utilization is better, if you’re using innovative therapies, you are seeing a better outcome in these patients.”
Looking forward, Dr. Jaberi-Douraki said, “artificial intelligence (AI) and machine learning will play a big role in helping us tackle and understand disease ... [AI] can handle the many different factors involved in the datasets, which could help us find the best regimens and potentially save lives.”
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Jaberi-Douraki M, Xu X, Raza S, et al. Global disparities in drug-related adverse events of patients with multiple myeloma: a pharmacovigilance study. Blood Cancer J. 2024;14(1):223.
