Association of medical comorbidities and cardiovascular disease with toxicity and survival in patients receiving checkpoint inhibitor immunotherapy.

Abstract

7039 Background: Checkpoint inhibitor immunotherapy (IO) is widely used to treat advanced cancer in pts. with medical comorbidities (MC), but the effect of MC on outcomes is poorly understood. Methods: We performed a single institution retrospective cohort study of pts. who received IO from 2011-2018. Immune-related adverse events (irAEs) were graded by Common Terminology for Adverse Events criteria, v4.0. MC were abstracted by query of ICD-10 codes corresponding to diagnoses in the Charlson Comorbidity Index (CCI) at any time prior to IO start. Modified CCI scores excluding points for cancer were calculated for each pt. Bivariate analysis with chi-squared statistics was used to describe characteristics and MC of pts. with vs. without irAEs. Overall survival (OS) was estimated by the Kaplan-Meier method (from start of first-line IO) and compared using the log-rank test. The association of CCI score and individual MC with irAEs and OS was tested with regression models adjusted for pt. characteristics. Results: Among 671 pts. with advanced cancer (39.6% melanoma; 21.8% non-small cell lung) treated with IO, median age 65 (IQR 55-74) years, the most common MC were COPD (24%) and diabetes (20%). 33.8% of pts. had CCI score ≥2. Neither CCI score nor any specific MC were associated with any grade or ≥G3 irAEs (P > 0.05). Increasing CCI score was significantly associated with decreased OS (P = 0.002). CHF (13.9 vs. 8.1 months, P = 0.008) and previous MI (14.2 vs. 10.1 months, P = 0.009) were associated with decreased median OS but did not remain significant in the regression model. Among pts. without cardiovascular disease (CVD), pts. with ≥G3 irAEs had longer OS than pts. with no ≥G3 irAEs (P < 0.001). This OS benefit for ≥G3 irAEs was not seen in pts. with CVD (P = 0.94). See table for adjusted HR. Conclusions: Risk for irAEs does not appear to be impacted by MC. Pts. with MC have shorter OS, but no specific MC are associated with OS after adjustment for pt. characteristics. OS is significantly increased among pts. without CVD who experience ≥G3 irAEs. CVD may be an important predictor of OS in pts. with irAEs and should be evaluated in patients receiving IO. [Table: see text]