A set of reproducible biomarkers are associated with better response rates to anti–PD-1 therapy in patients with advanced melanoma.
A set of reproducible biomarkers including the presence of metachronous metastases, CD163+ histiocytes at advancing edges, and NRAS mutations, among others, are associated with better response rates to anti–programmed death 1 (PD-1) therapy, and in some cases, with improved progression-free survival in patients with advanced melanoma, according to a new study. Using these biomarkers may help guide therapeutic decision making.
“Melanomas are highly immunogenic cancers, whose prognoses have been dramatically improved by immunotherapy,” wrote study authors led by BÃ©atrice Vergier, MD, of the HÃ´pital Haut-LÃ©vÃªque in France. Programmed death ligand 1 (PD-L1) expression is associated with better outcomes, but perhaps due to technical challenges in its evaluation, studies have consistently found some responses to anti–PD-1 therapy in PD-L1–negative tumors. The authors hypothesized that PD-L1 expression could be combined with other clinical, histological, and/or molecular criteria to better predict responses to the therapy.
They conducted a retrospective study on 70 metastatic melanoma patients (with a total of 118 melanoma samples) who received anti–PD-1 therapy. The cohort was 58.6% male, and 61.4% were over 60 years old; most patients received pembrolizumab (72.9%), with the remainder receiving nivolumab (27.1%). The results of the analysis were published in the British Journal of Cancer.
Patients who had metachronous metastases had a better 6-month objective response rate (ORR), at 35.3%, than those with synchronous metastases (P = .04). They also had a better 6-month overall survival rate, at 82% vs 36.8% (P = .002).
PD-L1 expression of greater than 5% was also associated with better ORR, at 35.7% vs 5% for < 5% expression (P = .02). Patients who had more than 10% CD163+ cells at advancing edges had a 6-month ORR of 34.3%, compared with 0% in those with < 10% (P = .009). Those who were NRAS mutation–positive had a 6-month ORR of 53.3%, compared with 19.6% in mutation-negative patients (P = .019). The researchers created a decision-tree algorithm using the factors with significant associations with ORR; it had a 40% sensitivity and a 94% specificity.
“According to our results, PD-L1 status alone cannot be used as a reliable biomarker of therapeutic response to anti–PD-1 immunotherapy but could be combined with other criteria,” the authors concluded. “Our findings highlighted the potential biomarker role of combining CD163+ histiocytes in melanomas and their metastases with other variables but need to be validated with a larger prospective cohort.”