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

ABSTRACT

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 (Tα1) 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 Tα1 to investigate the preconditioning role of Tα1 in imAbs-treated patients.

Methods: Records of patients with melanoma treated with Tα1 within a phase II trial and EAP program were reviewed comparing median OS among patients that sequentially received anti-CTLA-4 imAb and Tα1. Further, the effect of Tα1 on IPI long-term survivor patients was investigated.

Results: Among patients treated with Tα1, 21/61 patients received sequentially even anti CTLA-4 imAbs. Median OS at the data cut-off was 57.8 and 7.4 months in patients treated sequentially with anti-CTLA-4 imAbs or not, respectively. Moreover, pretreatment with Tα1 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 Tα1-treated patients. Moreover, an advantage in OS in patients sequentially treated with Tα1 and IPI was seen that suggests a synergistic effect.

KEYWORDS:

• CTLA-4
• checkpoint blockade
• long-term survival
• Thymosin alpha-1

Author contributions

RD was involved in conception, design, analysis and interpretation of the data, drafting of the paper. AMDG and MM were involved in conception and design of the data and final approval. FC, MA, and DG were involved in analysis and interpretation of the data, and final approval. VS and GB were involved in conception of the data and final approval. LC was involved in conception of the data, paper critically revising and final approval. RC and RD were involved in analysis of the data and final approval.

Declaration of interest

A. M. Di Giacomo received Honoraria from BMS, Roche and had a Consulting or Advisory role with Incyte, Pierre-Fabre. R. Camerini and R. Dragonetti are employees at Alfasigma SPA, R&D Dept. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosure

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper has been published as part of a supplement issue covering the proceedings of the Fifth International Symposium on Thymosins in Health and Disease and is funded by SciClone Pharmaceuticals.