Abstract
Background:Immune checkpoint inhibitors have dramatically changed the prognosis for patients with metastatic melanoma. However, not all patients respond to therapy and toxicities can be severe leaving need for reliable clinical predictive markers.Methods:We examined primary tumor characteristics including ulceration, BRAF mutation status, and Breslow depth in patients who subsequently developed stage IV disease and were treated with ipilimumab at 3 institutions. Patients in this study were not treated on clinical trials. To investigate the relationship between patient characteristics at the time of diagnosis and survival following melanoma diagnosis we utilized Cox proportional hazards models, accounting for delayed entry into the study cohort. Cox models estimate the age and institution adjusted hazard ratios for risk of death.Results:Of patients (n=385) treated with ipilimumab for stage IV melanoma, 302 met inclusion criteria. The complete response to ipilimumab was 5%, partial response was 13%, 18% had stable disease, 62% had progressive disease, and 5 unknown. The median overall survival rate was 2.03 years [95% confidence interval (CI): 0.13, 3.05]. Primary tumor Breslow depth, lymphovascular invasion, BRAF status, and ulceration did not predict sensitivity to ipilimumab. In this study patient cohort, BRAF mutation (adjusted hazard ratio: 1.43, 95% CI: 0.98, 2.07) and presence of ulceration (adjusted hazard ratio: 1.47, 95% CI: 0.95, 2.26) contributed to an increased risk of death.Conclusions:The presence of ulceration did not correlate with sensitivity to ipilimumab. Ulceration of the primary tumor and a BRAF mutation were moderately associated with worse survival in patients with metastatic melanoma treated with ipilimumab.
Highlights
Immune checkpoint inhibitors have dramatically changed the prognosis for patients with metastatic melanoma
Ipilimumab, a monoclonal antibody directed against the Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. aDivision of Surgical Oncology, bDepartment of Biomedical Informatics, Center for Biostatistics, The Ohio State University College of Medicine, Columbus, OH, cH
The aim of this study is to examine the relationship between primary tumor characteristics and survival in patients who developed metastatic disease and were treated with ipilimumab
Summary
Immune checkpoint inhibitors have dramatically changed the prognosis for patients with metastatic melanoma. Methods: We examined primary tumor characteristics including ulceration, BRAF mutation status, and Breslow depth in patients who subsequently developed stage IV disease and were treated with ipilimumab at 3 institutions. Ulceration of the primary tumor and a BRAF mutation were moderately associated with worse survival in patients with metastatic melanoma treated with ipilimumab. The rapid emergence of novel therapeutics in advanced melanoma, including immune checkpoint inhibitors such as ipilimumab and Programmed cell death protein 1 inhibitors has resulted in improved overall survival (OS)[2,3]. Response to immune checkpoint inhibitors seems to correlate with higher mutational load, though studies have been inconsistent[7,8] Melanoma is both a highly mutated and highly immunogenic tumor as evidenced by lymphocyte responses to primary melanoma and melanoma differentiation antigens[9]. This immunogenicity is thought to be related in part to the high mutational load in melanoma[7]
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