2018 ASCO News Highlights – Immuno-oncology Predictive Biomarkers
ASCO 2018 – Abstracts Related to IL-8 as a Biomarker and Target for Immunotherapy:
For a variety of treatment regimens, recent publications are reporting a significant reduction in the survival benefit for cancer patients that have elevated baseline blood levels of IL-8 protein.
Bristol Myers Squibb & collaborators reported at the 2018 ASCO conference a large cross sectional retrospective study of over 2,000 patients demonstrating that serum IL-8 is a promising clinical biomarker for patients that benefit from I-O therapy.
“Serum interleukin 8 (IL-8) may serve as a biomarker of response to immuno-oncology (I-O) therapy.” Carleton M, et al. poster 3025.
If high levels of IL-8 reduces the effectiveness of anti-PD-1 treatment, neutralization of IL-8 in combination with checkpoint blockade is an attractive combination therapy approach. Anti-IL-8 monotherapy was well tolerated and 73% of patients achieved stable disease in a Phase 1 trial of melanoma and NSCLC.
“Phase I trial of BMS-986253, an anti-IL-8 monoclonal antibody, in patients with metastatic or unresectable solid tumors.” Collins J, et al. poster 3091.
As a result of the above findings, BMS has initiated an IL-8 biomarker guided precision medicine Phase1/2b immuno-oncology trial.
"Phase 1b/2 study of nivolumab in combination with an anti–IL-8 monoclonal antibody, BMS-986253, in a biomarker-enriched population of patients with advanced cancer." Melero I, et al. poster TPS3109
IL-8 serum/plasma Levels & Understanding Treatment Response
IL-8 has several pro-tumorigenic properties:
- Promotes angiogenesis
- Attraction of MDSCs and Neutrophils
- Stimulation of Epithelial to Mesenchymal Transition (EMT)
The role of the chemokine IL-8 (CXCL8) in cancer and immuno-oncology has been lagging since mice do not have an IL-8 gene. High levels of serum IL-8 correlates with poor prognosis for a wide variety of:
- Treatment modalities (checkpoint inhibition, chemotherapy, and targeted therapies)
- Cancers (breast, colon, ovarian, prostate, melanoma, lung, kidney, hematological)
Historically, IL-8 has been associated with tumor burden, but in this new work by Carelton M. et. al., the correlation of baseline serum IL-8 with OS is independent of tumor burden or tumor PD-L1 expression. Baseline serum IL-8 is a promising biomarker of immunosuppression in the tumor microenvironment.
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