561 Influence of serotonergic and GABAergic agents on survival outcomes and adverse events related to immune checkpoint inhibitors

<h3>Background</h3> Serotonergic agents (selective serotonin and serotonin-norepinephrine reuptake inhibitors) and GABAergic agents (gabapentin and pregabalin) possess immunomodulatory properties. Serotonergic agents alter lymphocyte proliferation, suppress cytokine production and facilitate apoptosis.¹ Several types of immune cells express GABA receptors. GABA receptor signaling affects cytokine release, immune cell activation, migration and cytotoxicity.² We, therefore, evaluated the effect of serotonergic agents and GABAergic agents on survival outcomes in metastatic non-small cell lung cancer (mNSCLC) as well as immune-related adverse events (IRAEs) in various cancers with immune checkpoint inhibitors (ICI). <h3>Methods</h3> A retrospective cohort study of adult patients with metastatic cancers who received ICI with or without chemotherapy was conducted at a metropolitan safety net hospital from 1/2016 to 6/2022 after IRB approval. All patients and a subset of patients with mNSCLC were divided into two arms based on whether they were prescribed serotonergic agents during ICI therapy (SA vs. NS). Similarly, patients were grouped based on whether they received GABAergic agents during ICI therapy (GA vs. NG). Median overall survival (mOS), median progression-free survival (mPFS) per RECIST 1.1 and incidence of IRAEs were compared between the groups using multivariate logistic regression and alternative log-rank test adjusting for demographics, socioeconomic status, BMI, ECOG status, PD-L1 expression, tumor mutational burden, smoking, substance use and concurrent chemotherapy. <h3>Results</h3> 229 patients with various metastatic cancers received ICI therapy; 35% were African American, 6.5% were Hispanic, and 47% were female. There was no significant difference in the incidence of IRAEs (39% vs. 35%, p=0.632) between SA (n=66) and NS (n=163) arms. Furthermore, GA (n=62) and NG (n=167) arms had no significant difference in the incidence of IRAEs (42% vs. 34%, p=0.349). 110 patients had mNSCLC, of which 46% were female. Patients with mNSCLC in arm SA (n=28) had no significant difference in mOS (HR:1.02, CI 0.5–2.09, p=0.88) or mPFS (HR:1.12, CI 0.53–2.35, p=0.83) compared to patients in arm NS (n=82). Similarly, the two arms, GA (n=33) and NG (n=77), had no differences in mOS (HR:1.04, CI 0.57–1.89, p=0.77) or mPFS (HR:0.97, CI 0.49–1.93, p=0.64) for mNSCLC. <h3>Conclusions</h3> Serotonergic and GABAergic agents did not significantly affect survival outcomes for ICI therapy in mNSCLC or the occurrence of IRAEs with ICI therapy among various cancers. Serotonergic agents may be safely utilized for managing mood-related disorders in cancer patients on ICI therapy. Moreover, GABAergic agents are an appropriate option for pain control. Prospective studies are warranted to shed more insight. <h3>References</h3> Gobin V, Van Steendam K, Denys D, Deforce D. Selective serotonin reuptake inhibitors as a novel class of immunosuppressants. <i>Int Immunopharmacol</i> 2014;<b>20</b>(1):148–156. Bhandage AK, Barragan A. GABAergic signaling by cells of the immune system: more the rule than the exception. <i>Cellular and Molecular Life Sciences: CMLS</i> 2021;<b>78</b>(15):5667–5679. <h3>Ethics Approval</h3> The study obtained ethics approval from the University Health Truman Medical Center Institutional Review Board and the IRB approval number is 2016411.