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.
Dr. Goldstein is Emeritus Professor in the Department of Biochemistry and Molecular Medicine at The George Washington University School of Medicine in Washington, DC. He Chaired the Department from 1978 until March 2009. He is an authority on the thymus gland and the workings of the immune system, and co-discoverer (with Abraham White) of the Thymosins, a family of hormone-like peptides isolated from the thymus gland. Thymosina1(TA1) a molecule with immune enhancing properties, was the first of the Thymosins to enter clinical trials. It has been approved in China and 35 other countries, and has shown great promise in the treatment of severe sepsis, cancer, and a number of other diseases including? ?the potential treatment of cystic fibrosis. Most recentlyTA1 has been found to synergize with Ipilimumab(IPI) ,a check-point inhibitor & further extend the survival of Stage III/IV melanoma patients previously treated successfully with TA1 melanoma patients Thymosinβ4?(Tβ4), the second of the Thymosins to reach the clinic, has been shown to accelerate wound healing and the remodeling of injured tissues. ?Early Phase-II trials have been completed in patients with pressure and venostasis ulcers. Two Phase-III trials in? with dry eye and neurotrophic keratopathy have been completed in the US with promising results. A new Phase 3 trial in dry eye with 700 patients will begin in the fourth quarter of 2018An injectable form of Tb4?has been developed for internal indications such as myocardial infarction, stroke, multiple sclerosis, brain trauma and peripheral neuropathy. Dr. Goldstein’s research has helped define the role of biological response modifiers in health and disease, and has led to the discovery of important new links between the immune system, the neuroendocrine system and the brain.
He received his B.S. degree from Wagner College in 1959 and his M.S. and Ph.D. degrees from Rutgers University in 1964. He served on the faculties of the Albert Einstein College of Medicine from 1964 to 1972, and The University of Texas Medical Branch in Galveston from 1972 through 1978. Dr. Goldstein was the co-founder and first President and Scientific Director of The Institute for Advanced Studies in Aging and Geriatric Medicine (IASIA). He has also served as a member of the Board of Trustees of the Albert Sabin Vaccine Institute, as well as the Board of Directors of The George Washington University Cardiovascular Institute. He currently serves as the Chairman of the Board and Chief Scientific Advisor for RegeneRx Biopharmaceuticals, a public company developing novel wound healing and remodeling therapeutics.
Dr. Goldstein is the author of more than 445 scientific articles in professional journals, the inventor on over 25 U.S. and overseas patents, and the editor of several books in the fields of biochemistry, biomedicine, immunology and neuroscience. He is the recipient of several awards including the Career Scientist Award of the Health Research Council, City of New York; the Van Dyke Memorial Award in Pharmacology from the College of Physicians and Surgeons of Columbia University, a citation from the U.S. Department of Health, Education and Welfare “in recognition and appreciation of outstanding work in helping to establish a national program of ‘Biological Response Modifiers’”; a Doctor of Science Degree (Honoris Causa), Wagner College; the Decoration of the Order “Vasco Nunez De Balboa,” in the rank of Commander, Panama’s highest national honor for “contributions directed to the preservation of human life in the world”; the Distinguished Researcher Award of The George Washington University School of Medicine, and the “Chevalier des PalmesAcademiques,” for his scientific contributions to France.
Over the years, Dr. Goldstein’s laboratory has been a center for the training of graduate, medical, and postdoctoral students, many of whom are now continuing and expanding his studies on the role of the thymus in health and disease. Dr. Goldstein has also been a pioneer in medical education having developed a unique series of distance education programs presented for the Internet, called “Frontiers in Medicine.” This series of lectures and National Town Forums by leading scientists focused on research at the cutting edge. The broadcasts, which were presented “live” from The George Washington University, began in 1997 and were a first for continuing medical education on the Internet.