Abstract 6293: Influence of prescription opioids and recreational cannabis use on efficacy outcomes and adverse events related to immune checkpoint inhibitors

Abstract Introduction: Opioids and cannabis possess immunomodulatory properties. However, the effect of opioid receptor activity on immune function is complicated, facilitated by several mechanisms and can lead to enhancement or inhibition. Similarly, the relation between cannabinoid ligands of diverse types and endocannabinoid receptors on various immune cells is complex. We hereby delineate the effect of prescription opioids and recreational cannabis use on immune-related adverse events (IRAEs) during immune checkpoint inhibitor (ICI) therapy in various cancers, as well as efficacy outcomes in advanced non-small cell lung cancer (aNSCLC). Methods: This is a retrospective cohort study of adult patients with advanced cancers who received ICI with or without chemotherapy for at least two months at an urban safety net hospital from January 2016 to June 2022. All patients, as well as a subset of patients with aNSCLC, were divided into two arms based on whether they were prescribed opioids during ICI therapy or not (OP vs. NO). Similarly, they were grouped based on whether they reported recreational cannabis use during ICI therapy (since initiation of therapy) or not (CA vs. NC). Incidence of IRAEs, median overall survival (mOS) and median progression-free survival (mPFS) calculated per RECIST 1. 1 were the outcome variables. Multivariate logistic regression and alternative log-rank test were utilized for analysis with adjustments for demographics, insurance status, BMI, ECOG, PD-L1, TMB, smoking and concurrent chemotherapy. Results: 230 patients received ICI-based therapy; 47% were female, 34% were African American and 6. 5% were Hispanic. There was no significant difference in the incidence of IRAEs between OP (n=144) and NO (n=86; p=0. 225). However, CA (n=44) had higher IRAEs than NC (n=186) with an odds ratio estimate of 2. 023 (X2=4. 18, CI 1. 03-3. 97, p=0. 04). Among 110 patients with aNSCLC, 46% were female. Patients with aNSCLC in the OP arm (n=69) had no significant difference in mOS (HR=1. 34, CI 0. 8-2. 25, p=0. 26) or mPFS (HR=1. 21, CI 0. 69-2. 1, p=0. 51) compared to patients in the NO arm (n=51). Similarly, the two arms CA (n=21) and NC (n=89) had no difference in mOS (HR: 0. 96, CI 0. 5-1. 83, p=0. 89) or mPFS (HR: 1. 18, CI 0. 61-2. 29, p=0. 63) for aNSCLC. Conclusion: Recreational cannabis use during ICI therapy increased the incidence of IRAEs. Prescription opioids and recreational cannabis use did not significantly affect survival outcomes for ICI in aNSCLC. Prescription opioid use also did not significantly influence the occurrence of IRAEs. This study suggests that recreational cannabis may need to be used with caution in this patient population due to its influence on IRAEs. On the other hand, opioids appear to be a safe option for pain management in these patients. Larger studies are warranted to shed more insight into the effect of these substances on ICI therapy. Citation Format: Himil Mahadevia, Benjamin Eidenschink, An-Lin Cheng, Atharva Desai, Stephanie Harry, Lara Kujtan. Influence of prescription opioids and recreational cannabis use on efficacy outcomes and adverse events related to immune checkpoint inhibitors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 6293.