BACKGROUND: Radiotherapy combined with immunotherapy shows increasing efficacy in treating metastatic malignancies; however, positive outcomes may be negatively impacted by lymphocytopenia. Previous studies suggest thymosin α1 (Tα1) may mitigate radiation-induced lymphocytopenia. This study retrospectively evaluated the effects of a Tα1 loading dose on peripheral blood lymphocyte counts and assessed the safety and efficacy of radiotherapy combined with of PD-1 inhibitors in patients with advanced or refractory cancers. METHODS: A total of 48 patients received a 7-day loading dose of Tα1 (1.6 or 3.2 mg, once daily) followed by hypofractionated radiotherapy and PD-1 inhibitors. Peripheral blood T cells, B cells, and natural killer cells were quantified by flow cytometry before and after Tα1 treatment. The primary endpoint was the change from baseline in lymphocyte subset counts. Secondary endpoints included adverse events, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). RESULTS: The median follow-up was 13.7 months. Tα1 treatment for 7 days significantly increased the median counts of peripheral blood total T cells (422.5/μL to 614.0 /μL, P<0.001), CD4+ T cells (244.5/μL to 284.5/μL, P<0.001), and CD8+ T cells (159.0/μL to 222.5/μL, P<0.001). Among the 36 patients with evaluable data, the ORR was 19.4% and DCR was 69.4%. The median PFS and OS were 5.1 months and 9.6 months, respectively. Two patients (4.2%) experienced grade ≥3 treatment-related adverse events. CONCLUSION: A 7-day loading dose of Tα1 elevated lymphocyte counts in advanced cancer patients and was accompanied by satisfactory safety and efficacy profiles. It should be noted that the median follow-up of 13.7 months may be insufficient to fully assess long-term survival outcomes and the potential for late-onset toxicities. As this was an exploratory analysis across multiple tumor types, these findings warrant validation in larger, randomized studies with more homogenous cohorts.

Center for Cancer Diagnosis and Treatment The 2nd Affiliated Hospital of Soochow University Suzhou People's Republic of China

Center of PRaG Therapy The 2nd Affiliated Hospital of Soochow University Suzhou People's Republic of China

Laboratory for Combined Radiotherapy and Immunotherapy of Cancer The 2nd Affiliated Hospital of Soochow University Suzhou People's Republic of China

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