Evaluation of Prognostic Markers for Progression-Free Survival of Metastatic Melanoma Patients Treated with First-Line Ipilimumab Plus Nivolumab

Background: Combination checkpoint inhibitor therapy with ipilimumab plus nivolumab has significantly improved the treatment of patients with metastatic melanoma. This regimen has induced durable complete remissions and improved survival. However, these benefits are associated with a high risk of immune-related side effects. We evaluated the usefulness of potential prognostic biomarkers as predictors of eventual treatment benefit. Methods: A retrospective chart review was conducted of all metastatic melanoma patients treated by a single oncologist with ipilimumab plus nivolumab for advanced cutaneous or subungual melanoma. Baseline biomarkers including BRAF mutation status, serum lactate dehydrogenase levels, PD-L1 expression, and tumor mutation burden were correlated with progression-free survival (PFS). Results: Treatment outcomes were analyzed in 54 sequential patients. BRAF mutation status did not correlate with PFS. Only rare patients presented with an elevated lactate dehydrogenase (LDH); thus, this marker did not prove informative. There was a strong correlation of increased PD-L1 expression with treatment response, and an independent correlation of tumor mutation burden with prolonged PFS. An exploratory analysis suggested that the combination of low tumor cell PD-L1 expression and a low tumor mutation burden predicted a very poor immunotherapy response. Conclusions: Tumor mutation burden and PD-L1 represent potential prognostic biomarkers for response to combination CKI therapy, while LDH and BRAF offer limited prognostic value. Further work will be needed to develop a predictive nomogram to better aid in predicting potential treatment benefit.