1162P - Prolonged exposure to proton pump inhibitors (PPI) at the time of initiation of immune checkpoint blockade (ICB) mediates better clinical outcomes in patients with metastatic melanoma

Background

Tumor acidity negatively regulates tumor-specific effector T cells in the tumor microenvironment. Conflicting results emerged on the impact of PPI on the efficacy of ICB.

Methods

A retrospective analysis was conducted on patients (pts) with metastatic melanoma treated with ICB between 2019 and 2020 at the Christie NHS Foundation Trust. Data on demographics, sites of disease, performance status (PS), comorbidities, types of therapy, progression-free (PFS), and overall survival (OS) were collected. Statistical analyses were performed with univariable and multivariable Cox regression models. The aim was to define the association between PPI exposure (defined as 30 days before or after the initiation of ICB and for at least 21 days concomitant with ICB) and PFS, and OS.

Results

Data was collected on 189 pts with a median age of 60 years; 57.14% were male, 88% had ECOG PS 0/1, 17% were BRAF mutant, 28% had elevated serum LDH, and 28.5% had brain metastases. 162 (86%) pts received ICB as their first line of treatment for advanced disease. The majority of pts (92%) received ipilimumab and nivolumab, and 8% received pembrolizumab. 83 (44%) of pts were identified as PPI users with a median duration of PPI use concomitantly with ICB of 365 days (range 21-1976 days). PPI use was significantly associated with longer median PFS (not reached vs. 7.3 months, Hazard ratio (HR):0.53, 95%CI:0.35-0.79, p=0.002) and longer median OS (not reached vs. 17.2 months, HR:0.47, 95%CI:0.30-0.73, p=0.001). In a multivariable regression analysis accounting for age, gender, PS, Charlson comorbidity score, BRAF status, elevated LDH, brain and liver metastases, and line of treatment, the favorable impact of PPI use on PFS (HR:0.53, 95%CI:0.35-0.81, p=0.003) and OS (HR: 0.43, 95%CI:0.27-0.69, p<0.0001) was maintained.

Conclusions

Exposure to PPI for more than 21 days at the initiation of ICB mediates better clinical outcomes. Our findings suggest that the duration and timing of PPI use should be considered when investigating the impact on ICB outcomes. Prospective studies are required to test the priming effect of PPI on tumors with acidic microenvironments.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The Christie NHS Foundation Trust.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.