Thymosin α1 Elevates Lymphocyte Counts and Improves Immunoradiotherapy Outcomes in Patients with Advanced Cancer

Meiling Xu,1– 3,* Rongzheng Chen,1– 3,* Yuehong Kong,1– 3,* Junjun Zhang,1– 3 Pengfei Xing,1– 3 Xiangrong Zhao,1– 3 Liyuan Zhang1– 3 1Center of PRaG Therapy, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Center for Cancer Diagnosis and Treatment, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3Laboratory for Combined Radiotherapy and Immunotherapy of Cancer, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liyuan Zhang, Email [email protected]: Radiotherapy combined with immunotherapy shows increasing efficacy in treating metastatic malignancies; however, positive outcomes may be negatively impacted by lymphocytopenia. Previous studies suggest thymosin α 1 (Tα 1) may mitigate radiation-induced lymphocytopenia. This study retrospectively evaluated the effects of a Tα 1 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 Tα 1 (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 Tα 1 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. Tα 1 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 Tα 1 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.Keywords: LYMPHOCYTOPENIA, Radiotherapy, PD-1 inhibitor, thymosin α 1, loading dose, advanced cancer