Cancer Immunotherapy Side Effects Differ Sharply Across Racial Groups, Massive Data Analysis Reveals

Immune checkpoint inhibitors have transformed the treatment of many cancers, unleashing the body’s own defenses against tumors that once carried grim prognoses. But these powerful drugs come with a well-known catch: by removing the molecular brakes on T cells, they can also trigger the immune system to attack healthy tissue, producing immune-related adverse events that range from mild rashes to life-threatening inflammation of the heart, lungs or gut. A new analysis published in Nature Health suggests that this toxic burden is not distributed evenly. Drawing on data from nearly half a million clinical trials, a nationwide insurance database covering more than 80 million people, and a vast network of electronic health records, researchers report that the odds of experiencing these side effects differ significantly across racial groups — differences that have been largely invisible because the clinical trial enterprise itself rarely records who its patients are.

The study, led by Yuan Liu and Leng Han of the Indiana University School of Medicine together with colleagues including Eytan Ruppin, Douglas B. Johnson and Javid J. Moslehi, began with a sobering audit of the evidence base. Of the 487,688 trials listed on ClinicalTrials.gov up to March 2024, 97,254 were oncology-related and 7,274 involved immune checkpoint inhibitors. Yet only 210 of those immunotherapy trials — a mere 2.89 percent — included race information and enrolled more than 100 participants. The overwhelming majority, 86.77 percent, either lacked race information entirely or had enrolments too small to support meaningful comparisons. Most striking of all, among the 22 trials that enrolled at least 100 participants with more than 20 patients from each major racial group, not a single one reported adverse event data stratified by race.

To circumvent this data desert, the team turned to real-world evidence. They first mined Optum’s de-identified Clinformatics Data Mart Database, spanning 2007 to 2023 and encompassing 81.10 million insured individuals. Within it they identified 6.22 million patients with cancer diagnoses, of whom 91,852 received anti-PD-1 or anti-PD-L1 therapy: 1,979 Asian, 10,341 Black, 5,795 Hispanic and 65,907 white patients. Using diagnosis codes to capture immune-related adverse events arising after the start of checkpoint blockade, they documented 91,169 such events in 48,611 patients. After adjusting for age and sex with multivariable logistic regression, a clear pattern emerged: Black patients had higher odds of overall immune-related adverse events than Hispanic patients (odds ratio 1.08, 95 percent confidence interval 1.01 to 1.15), while Asian patients had lower odds than white patients (odds ratio 0.89, confidence interval 0.81 to 0.97).

Crucially, the findings did not rest on a single dataset. The team replicated the analysis in the National COVID Cohort Collaborative, a nationwide electronic health record resource containing data on 22.8 million individuals across 98 sites as of April 2024. The same directional patterns held: higher odds among Black patients compared with Hispanic patients, and lower odds among Asian patients compared with white patients. When the researchers stratified results by organ system using the MedDRA classification, aggregating adverse events into 13 system organ classes, they found that of 29 significant differences identified in the insurance database, 24 — 82.8 percent — showed consistent directional trends in the electronic health record cohort, a level of agreement that argues strongly against the results being statistical artifacts.

At the organ level, some of the differences were substantial. Black patients showed markedly higher odds of musculoskeletal and connective tissue disorders than Asian patients (odds ratio 1.44, confidence interval 1.30 to 1.60) and moderately higher odds than white patients (odds ratio 1.06). Conversely, Black patients had significantly lower odds of cardiac disorders than Asian patients (odds ratio 0.56, confidence interval 0.36 to 0.85), a finding with obvious clinical relevance given that checkpoint inhibitor myocarditis is among the most feared and fatal immune-related toxicities. When the analysis was further stratified by primary cancer site, the disparities sharpened: Black patients with stomach cancer had more than three times the odds of musculoskeletal disorders compared with Asian patients (odds ratio 3.31), white patients with liver cancer had lower odds of gastrointestinal disorders than Hispanic patients (odds ratio 0.68), and Black patients showed higher occurrence of nervous system disorders relative to Hispanic patients (odds ratio 1.42).

Drilling down to individual adverse event subtypes revealed even finer texture. Among 174 subtype-level comparisons tested in the insurance database, 60 showed differential odds across racial groups, and of the 56 that could be evaluated in the electronic health record cohort, 85.7 percent showed the same direction of effect. Arthritis stood out: Black patients had more than twice the odds of arthritis compared with Asian patients (odds ratio 2.27, confidence interval 1.92 to 2.68) and higher odds than white patients (odds ratio 1.27). Asian patients, by contrast, experienced significantly more rash than white patients (odds ratio 1.30), and in the validation cohort also showed higher rates of pruritus. In total, the researchers identified racial differences in 20 of the 29 immune-related adverse event types examined, indicating that the pattern is not confined to a handful of toxicities but pervades the entire spectrum of immunotherapy side effects.

Severity may differ as well. Because the real-world datasets do not natively record adverse event grades, the team used systemic steroid prescriptions as a proxy, following American Society of Clinical Oncology guidelines that recommend systemic steroids as first-line therapy for immune-related adverse events of at least grade 2. Among patients who experienced an adverse event, Black patients had the highest proportion of steroid exposure — 42.3 percent, compared with 39.9 percent for Hispanic and 39.2 percent for white patients — differences that reached statistical significance. The authors caution that drug claims do not specify why steroids were given, so the measure cannot pin severity to any particular toxicity, but it suggests that Black patients may shoulder a greater burden of serious, treatment-altering side effects.

The team also worked to rule out alternative explanations. A concern with any claims-based study is that differences in reporting or care patterns, rather than biology, might drive the results. To test this, they classified providers by patient composition and compared the average number of adverse events recorded per patient: providers predominantly serving white patients averaged 2.89 events per patient versus 2.88 for those predominantly serving non-white patients — no significant difference. Sensitivity analyses adjusting for comorbidities, neighborhood-level socioeconomic indicators and prior cancer treatments preserved the findings, with 89.1 percent of re-tested associations keeping the same direction of effect, a concordance significantly exceeding chance. Still, the authors are careful to note that the study is retrospective and observational, reflecting associations rather than proven causal relationships, and that residual confounding cannot be excluded.

Perhaps the most important caveat concerns what race actually represents. The authors emphasize that race is a social construct rather than a strictly biological variable, and that the observed disparities may reflect a tangle of influences: genetic variation in immune regulation, differences in tumor-immune interactions, unequal healthcare access, environmental exposures, surveillance intensity and the enduring effects of structural racism on diagnosis and treatment. They also note the limits of their data — the insurance database records race and ethnicity as a single combined variable, patients outside the four largest groups were too few to analyze, and the findings may apply most directly to patients covered by the insurer studied. Translating population-level patterns into individual clinical decisions, they warn, must be done cautiously to avoid entrenching the very disparities the work exposes.

What the study makes unmistakably clear is that the current system is flying blind. With 87.3 percent of checkpoint inhibitor trials on ClinicalTrials.gov conducted in the United States, where white patients dominate enrolment — even the landmark KEYNOTE-001 pembrolizumab trial, with 1,260 enrollees, counted only 63 Hispanic and 26 Black participants in total — safety signals in minority populations are systematically under-represented. Real-world datasets with millions of patients may be the only practical way to detect these differences. The authors call for racial diversity in both clinical trials and post-marketing surveillance, and for adverse events to be systematically recorded in a race-stratified manner. As immunotherapy reaches a growing share of the roughly 90,000 insured patients now treated annually, ensuring that its benefits and risks are understood — and managed — equitably across all populations has become not just a scientific imperative but a matter of basic fairness in cancer care.

Subject of Research: Racial disparities in immune-related adverse events during immune checkpoint inhibitor cancer therapy

Article Title: Disparities in adverse events during cancer immunotherapy

Article References: Liu, Y., Luo, M., Yang, J., Chen, Y., Zhang, P., Su, J., Huang, K., Salem, J.-E., Diao, L., Bian, J., Ruppin, E., Johnson, D. B., Moslehi, J. J., Han, L., on behalf of N3C, & Chute, C. G. (2026). Disparities in adverse events during cancer immunotherapy. Nature Health. https://doi.org/10.1038/s44360-026-00201-2

Image Credits: AI Generated

DOI: 10.1038/s44360-026-00201-2

Keywords: cancer immunotherapy, immune checkpoint inhibitors, immune-related adverse events, racial disparities, health equity, clinical trials, real-world data, PD-1 inhibitors, arthritis, pharmacovigilance, electronic health records, oncology