Soluble CD163 Potential Biomarker in Advanced Cutaneous Melanoma

Patients with advanced cutaneous melanoma who are responsive to nivolumab (Opdivo) have higher serum levels of soluble CD163 (sCD163) compared with nonresponders, according to the results of a recent study.

The introduction of anti—PD-1 antibodies such as nivolumab and pembrolizumab (Keytruda) have greatly increased survival rates in multiple types of cancers, including advanced melanoma. With the addition of ipilimumab (Yervoy), a cytotoxic T-lymphocyte antigen (CTLA-4) monoclonal antibody, researchers have found that responses are even better in patients who responded to nivolumab. However, in patients with nivolumab-resistant melanoma, the efficacy of ipilimumab is significantly lower, emphasizing the need for a predictive biomarker that can enable researchers to identify which patients should receive both therapies.

Tumor-associated macrophages are immune cells involved in maintaining tumor environment, with PD-1 expression being one of the key factors. In skin cancer, CD163 macrophages are the main population of tumor-associated macrophages. After administration of an anti—PD-1 antibody, soluble clusters of CD163 appear in the serum, making it a useful predictive biomarker for anti–PD-1 therapy. The study authors analyzed serum levels of sCD163 in 76 patients with advanced cutaneous/noncutaneous melanoma treated with nivolumab to determine if serum sCD163 was a potential predictive biomarker for melanoma.

The study population included 59 patients with advanced cutaneous melanoma and 16 patients with advanced noncutaneous melanoma treated with nivolumab. Of the 59 patients with cutaneous melanoma, the objective response rate (ORR) was 22%, there was 1 complete response (CR), 12 partial responses (PR), 16 stable disease (SD), and 29 progressive disease (PD). The ORR for the 16 patients with noncutaneous melanoma was 25%, with 4 PR, 5 SD, and 7 PD.

Serum sCD163 levels in patients with advanced cutaneous melanoma significantly increased from baseline (P < .0001); however, no significant difference in serum sCD163 levels were seen in patients with advanced noncutaneous melanoma. Thresholds to distinguish responders from nonresponders were determined to be 3.07 ± 0.07 ng/mL for cutaneous melanoma and 0.47 ± 0.05 ng/mL for noncutaneous melanoma.

The mean change ratio of sCD163 serum levels were higher for responders in patients with cutaneous melanoma (144.6%) compared with nonresponders (101.0%). In contrast, nonresponders with noncutaneous melanoma (122.3%) had higher mean change ratio in sCD163 serum levels compared with responders (84.1%). Sensitivity and specificity for serum sCD163 in cutaneous melanoma were 84.6% and 87.0%, respectively (P = .003), and 100.0% and 66.7% for non-cutaneous melanoma, respectively (P = .3154).

The study authors found that for patients that do not respond to nivolumab, the addition of ipilimumab provides minimal benefits and increases the risk of immune-related adverse events. In patients with advanced cutaneous melanoma, an increase in serum sCD163 levels appears to be associated with responders, making it a viable predictive biomarker in this population. Although serum sCD163 levels seem to be a useful predictive biomarker in patients with advanced cutaneous melanoma treated with nivolumab, further studies with larger cohorts are needed to substantiate these results.

Reference

Fujimura T, Sato Y, Tanita K, et al. Serum level of soluble CD163 may be a predictive marker of the effectiveness of nivolumab in patients with advanced cutaneous melanoma. Front Oncol. 2018;8:530. doi: 10.3389/fonc.2018.00530.