Background: Comorbidities are more prevalent among older adults and predict worse outcomes for cytotoxic chemotherapy. Immunotherapies are increasingly used to treat various cancers and have a milder but less predictable toxicity profile. This study aimed to evaluate the association of comorbidity burden with immune-related adverse events (irAEs) and survival among older adults treated with these immunotherapies for any cancer type. Methods: We created a retrospective registry of consecutive patients ≥ 70 years old treated with one or more doses of an immune checkpoint inhibitor for any cancer indication between 2/1/2011- 4/7/2022 at our comprehensive cancer center. Treatment outcomes, including treatment-emergent adverse events, were captured via chart review. The comorbidity burden at the time of immunotherapy initiation was captured by chart abstraction and classified using the Charlson Comorbidity Index (CCI). We compared patients with high CCI scores (≥ 4) to patients with low CCI scores (CCI <4) on the outcome of any irAE yes/no, using chi-square tests. We used the Kaplan-Meier method to compare progression-free survival (PFS) and overall survival (OS) between the two CCI groups. Survival analyses were calculated from the first dose of immunotherapy to death, last follow-up, or disease progression. A two-sided alpha of 0.05 was used for analyses. The study had institutional IRB approval. Results: Our cohort consisted of 1,216 patients (median age 76 years [interquartile range 73 to 80]), of which 217 (18%) had a high CCI score. The most common comorbidities were chronic obstructive lung disease (45%), coronary artery disease (29%), and diabetes (29%). The most common cancer type was lung cancer (46%), followed by melanoma (15%). Patients with a high CCI score had a shorter median overall survival than patients with a low CCI (11.2 vs. 13.8 months, respectively, p = 0.049). However, there was no significant difference in PFS between the high and low CCI groups (median PFS 27.1 vs. 25.0 months, p=0.32). There was no association between the CCI group and the incidence of any-grade irAEs (39% vs. 40%, p = 0.82). There was also no association between CCI group and high-grade (grade ≥3) irAEs (17% vs. 15%, p = 0.35). We did not find any associations between any individual CCI comorbid condition and risk of irAE.¹Conclusions: A high comorbidity burden, as measured by the CCI, was not associated with increased immunotherapy toxicity or shorter PFS among older adults. The presence of comorbidities was associated with shorter OS. These data can support informed decision-making for older adults with comorbidity considering immunotherapy. Reference: 1. Charlson ME, Carrozzino D, Guidi J, Patierno C. Charlson Comorbidity Index: A Critical Review of Clinimetric Properties. Psychother Psychosom. 2022;91(1):8-35. doi: 10.1159/000521288. Epub 2022 Jan 6. PMID: 34991091.