A single-institution experience of pneumonitis in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors.
Authors: Masur Jack , Ali Soham , Fortune Kathryn , Bueno Juliana , Battey Thomas , Mullapudi Abhishek , Goudarzi Ariaz , Patel Hitesh , Sturek Jeffrey , Devitt Michael Edward , Skelton William Paul , Dreicer Robert , Viscuse Paul Vincent 
Published: February 2025

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Background:
Immunotherapy (IO) has dramatically changed the treatment landscape for patients with metastatic renal cell carcinoma (mRCC). The expanded use of IO in mRCC has led to an increased risk of immune-related adverse events (irAEs) in this population. Pneumonitis is an uncommon but potentially fatal irAE. Data describing the incidence of pneumonitis among mRCC patients treated with IO are sparse and the clinical experience of these patients is not widely described.
Methods:
We retrospectively identified patients with mRCC who received IO therapy at the University of Virginia and investigated the incidence of pneumonitis in this population. Clinical, radiologic, and pathologic features of pneumonitis were collected and analyzed by a multidisciplinary team of medical oncologists, pulmonologists, and radiologists. Images were reviewed by two independent radiologists. Associations among pneumonitis incidence, therapy received, and patient characteristics were examined using univariate regression models with p-values adjusted using the Benjamini-Hochberg algorithm, as well as associations between clinical and radiologic features of pneumonitis and outcomes.
Results:
Data were available for 146 patients with mRCC who received IO as first- (n=117) or second- (n=29) line treatment. The overall incidence of pneumonitis in our cohort was 8.9%. Pneumonitis occurred in 9.4% of patients who received IO as first line therapy and 6.9% of second line. Incidence was 10.8% among those treated with IO/IO, 10% with IO/TKI, and 4.7% with IO monotherapy. Fifty-four percent of patients who developed pneumonitis had received prior chest radiation vs 11% who did not develop pneumonitis (p-adj: 0.014). Eight of the 13 pneumonitis cases (61.5%) were grade 1 to 2, and 85% improved/resolved with drug holding and/or steroid administration. Five patients were rechallenged with IO and two experienced recurrent pneumonitis; both cases were grade 2 and resolved with oral steroids. Two patients worsened clinically after initial pneumonitis diagnosis and died during management; cause of death was attributable to pneumonitis in one patient and multifactorial in the other. Radiologic and pathologic features of pneumonitis were diverse and not significantly associated with severity or clinical outcome.
Conclusions:
Our study describes the variable clinical, radiologic, and pathologic characteristics of IO-associated pneumonitis in a single institution mRCC population. Our analysis suggests that incidence of pneumonitis in our mRCC population may be associated with prior receipt of chest radiation. Most cases of pneumonitis in our study were mild and successfully managed, however two patients had worsening symptoms despite escalating treatment and did not survive. Broader investigation of the incidence, causes, and clinical experience of pneumonitis in mRCC is needed.