Background: Previous studies indicated the evidence that baseline levels of thyroid antibodies, thyroid status, and serum lactate dehydrogenase (LDH) and M stage may influence the prognosis of patients with advanced or metastatic melanoma treated with immune checkpoint inhibitors that targets programmed cell death-1 (PD-1) or programmed death ligand 1, which reported that dramatic improvements in survival rates were observed; however, the presence of controversy has prevented consensus from being reached. Study objectives were to develop a nomogram to identify several prognostic factors in Chinese patients with metastatic melanoma receiving immunotherapy.
Methods: This retrospective study included 231 patients from Sun Yat-sen University Cancer Center, and patients were split into internal cohort (n = 165) and external validation cohort (n = 66). We developed a nomogram for the prediction of response and prognosis on the basis of the levels of serum thyroid peroxidase antibody (A-TPO), free T3 (FT3), and LDH and M stage that were measured at the baseline of anti-PD-1 infusion. In addition, the follow-up lasted at least until 5 years after the treatment or mortality. RECIST v1.1 was used to classify treatment responses.
Results: Chi-square test showed that PD-1 antibody was more effective in patients with melanoma with high level baseline FT4 or earlier M stage. A multivariate Cox analysis showed that baseline FT3 (P = 0.009), baseline A-TPO (P = 0.016), and LDH (P = 0.013) levels and M stage (P < 0.001) independently predicted overall survival (OS) in patients with melanoma. The above factors are integrated, and a prediction model is established, i.e., nomogram. Survival probability area-under-the-curve values of 1, 2, and 3 years in the training, internal validation, and external validation cohorts showed the prognostic accuracy and clinical applicability of nomogram (training: 0.714, 0.757, and 0.764; internal validation: 0.7171963, 0.756549, and 0.7651486; external validation: 0.748, 0.710, and 0.856). In addition, the OS of low-risk (total score ≤ 142.65) versus high-risk (total score > 142.65) patients varied significantly in both training group (P < 0.0001) and external validation cohort (P = 0.0012).
Conclusions: According to this study, baseline biomarkers are associated with response to immunotherapy and prognosis among patients with metastatic melanoma. Treatment regimens can be tailor-made on the basis of these biomarkers.
Keywords: anti-pd-1 treatment; baseline indicators; immunotherapy; metastatic melanoma; nomogram.
Copyright © 2022 Zhao, Li, Xie, Deng, Wen, Li, Wu, Yang, Li, Tang, Zhang and Ding.