When immunity backfires: Meta-analysis on sarcoidosis reactivation in cancer patients treated with immune checkpoint...

The use of immune checkpoint inhibitors (ICIs) in patients with pre-existing sarcoidosis raises concerns about disease reactivation. However, the incidence and clinical implications of sarcoidosis flare under ICI therapy remain poorly defined. Given the rarity of this scenario and limited reported events, this quantitative synthesis aimed to provide an exploratory summary of the available evidence and its uncertainty.

A pooled analysis included seven published studies, primarily retrospective cohorts and case series, comprising 43 cancer patients with documented pre-existing sarcoidosis treated with ICIs. Data on flare occurrence, ICI class, management, and oncologic outcomes were extracted. The pooled prevalence of flare was estimated using a random-effects model with logit transformation and continuity correction. Sensitivity analyses for rare events included exact binomial confidence intervals around the crude proportion and an alternative pooled estimate without continuity correction. Heterogeneity was assessed using Cochran's Q, I², and τ² statistics.

Overall, 93.0% of patients showed no reactivation. The pooled prevalence of flare was 19.6% (95% CI: 8.1-40.3) with low heterogeneity (Q = 7.00, p = 0.32; I² = 14.3%; τ² = 0.27). Flares were mild to moderate and managed with corticosteroids, rarely requiring permanent discontinuation. Subgroup analysis showed higher flare rates with anti-CTLA-4 inhibitors (25%) compared with anti-PD-1/PD-L1 agents (14.3%) and mixed regimens (3.1%). No fatal or irreversible reactivations were reported.

Sarcoidosis flare under ICI therapy appears uncommon and generally manageable; however, prevalence estimates should be interpreted as exploratory given sparse event count.