Clinical associations of cannabis use among patients receiving immune checkpoint inhibitors: A real-world analysis.

Abstract

11143 Background: Cannabis use is common in patients with cancer, yet its clinical associations during immune checkpoint inhibitor (ICI) therapy is poorly defined. We evaluated the association between documented cannabis use and clinical outcomes among patients receiving ICIs. Methods: We conducted a retrospective cohort study of adults ≥18 years in the TriNetX US Collaborative Network with advanced or metastatic solid tumors treated with ICIs since January 1, 2019. Cannabis exposure was defined by diagnostic codes for cannabis-related disorders or prescriptions for cannabis-derived products documented 3 months prior to 2 years after ICI start. Patients who died in 60 days were excluded. Primary outcome was 3-year overall survival (OS); secondary outcomes included 2-year inpatient and emergency department (ED) visit, with joint sprain as a negative control outcome. Propensity matching adjusted for demographics, comorbidities, cancer type and stage, and tobacco and alcohol use. Hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (CI) and Kaplan–Meier analyses were calculated. Results: After matching, 3,634 patients were included in the OS cohort. Patients with no documented cannabis use had significantly higher 3-year OS and median survival versus cannabis users (HR 0.67; 95% CI 0.63-0.72; median OS 34.8 vs 18.7 months). This association was observed across all tumor subgroups except head and neck squamous cell carcinoma (HNSCC) (Table 1). Among 2,855 matched patients in the healthcare utilization cohort, patients without cannabis use had lower healthcare utilization within 2 years, including fewer ED visits (RR 0.83; 95% CI 0.79-0.87) and inpatient admissions (RR=0.82; 95% CI 0.79-0.84). These findings were consistent across subgroups except for ED visits in HNSCC (Table 1). Joint sprain showed no association with cannabis exposure (RR 0.93, 95% CI 0.64-1.35). Conclusions: Cannabis use during ICI therapy was associated with lower survival and higher healthcare utilization in multiple solid tumors. This may reflect unmeasured symptom burden or clinical vulnerability but also raises the hypothesis of a potential interaction between cannabis exposure and ICI therapy. Prospective studies incorporating symptom severity, dose, timing, and route of exposure are needed to clarify these relationships. Clinical outcomes by cannabis exposure. Group Overall survival HR (95% CI) OSp-value ED Visit RR (95% CI) EDp-value Inpatient visit RR (95% CI) Inpatient visitp-value Overall 0.67 (0.63–0.72) <0.01* 0.83 (0.79–0.87) <0.01* 0.82 (0.79–0.84) <0.01* NSCLC 0.73 (0.68–0.79) <0.01* 0.85 (0.81–0.90) <0.01* 0.85 (0.82–0.89) <0.01* RCC 0.60 (0.50–0.73) <0.01* 0.81 (0.73–0.91) <0.01* 0.78 (0.72–0.85) <0.01* Melanoma 0.52 (0.40–0.69) <0.01* 0.70 (0.59–0.83) <0.01* 0.73 (0.65–0.82) <0.01* HNSCC 0.93 (0.74–1.16) 0.52 1.05 (0.89–1.25) 0.56 0.87 (0.77–0.98) 0.02* *Statistically significant (p < 0.05).