Hematologic and solid-organ malignancy risk in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.

BACKGROUND

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare autoimmune disease characterized by small- and medium-vessel inflammation. Although chronic immune dysregulation and cytotoxic therapy exposure have been hypothesized to increase malignancy risk, large-scale, real-world evidence quantifying these risks has been limited. This study aimed to characterize hematologic and solid-organ malignancy risk profiles in patients with AAV using a large, multi-institutional database.

METHODS

We conducted a retrospective cohort study using the TriNetX Research Network, using de-identified electronic medical record data from 2014 to 2024. We identified 19,238 patients with AAV and performed 1:1 propensity score matching to seborrheic keratosis controls on demographic and clinical covariates, yielding 18,255 matched pairs. Five-year incidences of hematologic and solid-organ malignancies were compared using hazard ratios (HR) and 95% confidence intervals (95% CI) from Cox proportional hazards regressions.

RESULTS

Here we show that patients with AAV have a significantly increased risk of overall cancer (HR 1.23; 95% CI 1.12-1.35), driven by higher rates of hematologic malignancies (HR 2.12; 95% CI 1.77-2.53) and specific solid-organ cancers including lung (HR 1.78), bladder (HR 1.99), brain (HR 2.22), and lip/oral cavity/pharyngeal cancers (HR 1.78). Myelodysplastic syndromes (HR 4.11) and leukemia (HR 2.72) show the strongest associations. Negative controls show no risk elevation.

CONCLUSIONS

Patients with AAV face distinct and heightened risks for select hematologic and solid-organ malignancies, supporting the need for tailored cancer surveillance strategies. These findings provide a large-scale, real-world evidence base for malignancy risk stratification and proactive screening in AAV.