Peripheral and local predictive immune signatures identified in a phase II trial of ipilimumab with carboplatin/paclitaxel in unresectable stage III or stage IV melanoma
Journal for ImmunoTherapy of Cancer Dec 01, 2017
Jamal R, et al. - Researchers in this phase II trial combined ipilimumab with carboplatin/paclitaxel (CP) to assess its safety, efficacy, and to search for peripheral and tumor-based predictive biomarkers in unresectable stage III or stage IV melanoma. In this trial, the combination of ipilimumab and CP was well tolerated and indicated novel characteristics in association with patients likely to benefit from treatment. Poor patient outcomes seemed to have a strong correlation with a pre-existing systemic inflammatory state characterized by elevation of selected chemokines and advanced B cell differentiation, revealing potential predictive circulating biomarkers.
Methods
- With ipilimumab and CP, researchers treated 30 patients with untreated unresectable/metastatic melanoma.
- They monitored adverse events (AEs) and evaluated response to treatment.
- They collected tumor tissue and peripheral blood at specified time points to characterize tumor immune markers by immunohistochemistry and systemic immune activity by multiplex assays and flow cytometry.
Results
- All 5 cycles of CP were received by 83% of patients and ipilimumab induction was completed by 93%.
- In 13% of patients, researchers noticed serious AEs; no treatment-related deaths were observed.
- In this study, best Overall Response Rate (BORR) and Disease Control Rate (DCR) were 27 and 57%, respectively.
- Median overall survival of 16.2 months was noticed.
- They observed a positive correlation between response to treatment and a higher tumor CD3+ infiltrate (immune score) at baseline.
- Patients who experienced clinical benefit indicated NRAS and BRAF mutations were less frequent.
- On assessing peripheral blood, it was noticed that non-responders had elevated baseline levels of CXCL8 and CCL4, and a higher proportion of circulating late differentiated B cells.
- They observed strong association of pre-existing high levels of chemokines (CCL3, CCL4 and CXCL8) and advanced B cell differentiation with worse patient overall survival.
- During treatment, elevated proportions of circulating CD8+/PD-1+ T cells seemed associated with worse survival.
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