Long-term follow up of metastatic melanoma patients treated with Thymosin alpha-1: investigating immune checkpoints synergy

Background: Immune checkpoint blockade antibodies (imAbs), such as the anti Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) ipilimumab (IPI) raised overall survival (OS) in metastatic melanoma (MM). Further, long-term OS is a crucial endpoint in MM. Thymosin alpha-1 (T1) with dacarbazine (DTIC) showed activity in a phase II trial and a compassionate use program (EAP). We report on long-term follow-up of patients treated with T1 to investigate the preconditioning role of T1 in imAbs-treated patients.Methods: Records of patients with melanoma treated with T1 within a phase II trial and EAP program were reviewed comparing median OS among patients that sequentially received anti-CTLA-4 imAb and T1. Further, the effect of T1 on IPI long-term survivor patients was investigated.Results: Among patients treated with T1, 21/61 patients received sequentially even anti CTLA-4 imAbs. Median OS at the data cut-off was 57.8 and 7.4months in patients treated sequentially with anti-CTLA-4 imAbs or not, respectively. Moreover, pretreatment with T1 in all (95) IPI-evaluable patients confirmed a significant increase in long-term OS.Conclusion: This is the first report on long-term follow-up of T1-treated patients. Moreover, an advantage in OS in patients sequentially treated with T1 and IPI was seen that suggests a synergistic effect.