Serum vitamin B12 levels and response to immunotherapy.

Abstract

e14542 Background: Underlying metabolic pathways have a role in regulation of response to cancer immunotherapy. Due to its immunomodulatory properties, we sought to investigate the relationship between elevated serum vitamin B12 (VitB12) and survival among individuals with cancer treated with immune checkpoint inhibitors. Methods: Data from a retrospective chart review were used to identify patients with advanced cancer initiating anti-neoplastic treatment and a concomitant VitB12 measurement (elevated: > 820 ng/L), between 1/2010-1/2022 at our institution. Patients on immunotherapy (IO) and other regimens (control) were compared using Mann-Whitney test for continuous variables, and Chi-square test or Fisher's test for categorical variables. Multivariate Cox regression models were used to assess the effect of VitB12 levels on overall survival (OS) and progression free survival (PFS), with adjustment for potential confounders. Results: A total of 501 patients were included (control, n = 408; IO, n = 93). Groups were well balanced for treatment line (first line, 91.4% vs. 94%), VitB12 levels (elevated, 29.9% vs. 23.7%; mean, 762.4 ng/L vs. 687.6 ng/L) and liver function tests. Cancer diagnoses differed between groups (most common, gastrointestinal vs. lung, p < 0.001). Multivariate analysis revealed that high VitB12 was negatively associated with OS in both groups (control: hazard ratio, HR 1.4, 95% CI 1.01-1.96, p = 0.04; IO: HR 2.74 as sum of linear baseline and interaction effects, in log scale), as were age (HR 1.03, 95% CI 1.02-1.04, p < 0.01), male gender (HR 0.66, 95% CI 0.50-0.88, p < 0.01), and neutrophil to lymphocyte ratio (NLR) (HR 1.05, 95% CI 0.48-0.99, p = 0.01). However, the only negative prognostic factor for PFS was VitB12 in the IO group alone (calculated HR 8.34). No association was observed with patient and cancer characteristics, other laboratory values, chemotherapy (p = 0.3) or biologic therapy (p = 0.8). Mean follow-up in the control and IO groups was 93 vs 54 weeks (OS), and 22 vs 33 weeks (PFS), respectively. Conclusions: Elevated VitB12 levels were negatively associated with response to immune checkpoint inhibitors, independently of other prognostic factors such as age, cancer type, treatment line and NLR. In addition to a direct role in cellular immunity, VitB12 is involved in gut microbiota balance, which in turn affects host immune responses – suggesting a possible immune-metabolic interplay. Further research is needed to elucidate the metabolic regulators of response to immunotherapy and potential strategies of intervention, in order to rationalize and broaden its clinical utility.