2539 - Postmarketing Surveillance of Adverse Events after Immune Checkpoint Inhibitor Therapy and Radiotherapy

Purpose/Objective(s): Immune checkpoint inhibitors (ICIs) are important for cancer treatment with increasing expansion of indications to early-stages and in adjuvant settings. However, they are associated with a wide range of significant adverse events (AEs). Patients undergoing radiotherapy (RT) in proximity to ICI administration are at risk for AEs of both ICI and RT. We hypothesized that patients starting RT during their first ICI course (Early RT), meaning starting concurrent RT and ICI, were at higher risk of AEs as compared to patients starting RT after their first ICI course (Late RT).

Materials/Methods: We identified 448 patients = 21 years, diagnosed with = 1 malignancy prior to starting their first ICI between 2016 and 2023 at our institution with available start and end ICI course dates who had an outpatient visit in the 550 days prior to ICI start, and started an RT course at our institution after ICI start. Early RT was defined as starting RT during the first ICI course. Late RT was defined as starting an RT course after the first ICI course. AE development dates were identified with ICD10 codes assigned after RT start; for endocrine AEs, new relevant prescription was also considered for the AE date. For each AE (thyroid disorder, adrenal disorder, type I diabetes, or pneumonitis), patients with an AE-like disorder diagnosed prior to RT start were excluded from the analysis, and a complete case multivariable Cox proportional hazards model was fit comparing Late to Early RT with follow-up starting at RT start, adjusting for sex, age, and Charlson co-morbidity index at RT start, and AJCC8 clinical tumor stage of the malignant diagnosis closest to and before ICI start.

Results: Of 448 patients, 179 were Early RT (269 Late RT), mean age was 70 years (SD 13, range 21-98 years), 52% were female (48% male), self-reported race was 81% White, 8% Black or African American, 5% Asian, 0.4% Pacific Islander, and 5% missing, mean comorbidity score was 9 (SD 2.3), stage was 46% IV, 17% III, 10% II, 14% I, 1% 0, and 12% missing, and the primary malignant diagnosis closest to and before ICI start was 45% lung, bronchus, or pleura, 14% genitourinary, 9% gastrointestinal, 8% gynecological, 6% head and neck, 6% skin, 6% breast, 3% leukemia or lymphoma, 2% bone or soft tissue, and 1% central nervous system. We did not find an association between Late versus Early RT and the development of thyroid (290 patients, HR 0.94, 95% CI 0.37-2.38, p=0.90), adrenal (359 patients, HR 0.84, 95% CI 0.24-2.88, p=0.78), type I diabetes (371 patients, HR 0.63, 95% CI 0.15-2.63, p=0.53), or pneumonitis (154 patients, HR 1.13, 0.82-1.56, p=0.44) AEs.

Conclusion: In this post-marketing surveillance study of 448 patients undergoing first ICI and then RT, starting RT during the ICI course was not associated with increased risk of thyroid disorder, adrenal disorder, type 1 diabetes, or pneumonitis AEs compared to starting RT after the ICI course. This real-world data adds to clinical trial data. Further investigation includes consideration of later ICI courses.