Immune Checkpoint Inhibitor-Associated Pneumonitis in Patients Treated for Metastatic Renal Cell Carcinoma

Abstract

Immune checkpoint inhibitors (ICIs) improve outcomes in metastatic renal cell carcinoma (mRCC) but may be associated with pneumonitis. We retrospectively studied adults with mRCC who began first- or second-line ICI therapy at the University of Virginia Medical Center between 2015 and 2023. Potential cases underwent multidisciplinary clinical review, and two thoracic radiologists independently reviewed available computed tomography scans. Among 146 ICI-treated patients, 13 developed pneumonitis (8.9%; 95% CI 4.8–14.7%). Incidence did not differ significantly by treatment line or ICI regimen. Incidence was higher with prior chest radiation than without (31.8% vs. 4.8%; unadjusted odds ratio 9.2, 95% CI 2.7–31.0; Benjamini–Hochberg-adjusted p = 0.005). Five cases (38%) were grade 3–4 at diagnosis, and seven (54%) reached grade ≥ 3. Nine patients (69%) received high-dose systemic corticosteroids. Eleven patients (85%) improved or resolved with initial management; two, both with grade 1–2 pneumonitis at diagnosis, worsened and died (grade 5). Five patients underwent ICI rechallenge after clinical recovery, without recurrent pneumonitis. In this exploratory cohort, pneumonitis was sometimes fatal despite a low grade at presentation. The association with prior chest radiation is hypothesis-generating and warrants evaluation in larger studies with detailed radiation and confounder data.