Combining SBRT with GM-CSF and Peg-IFNα to induce abscopal effects in previously treated patients with metastatic thymic tumors: A single-institution, phase II trial.

Abstract

8121 Background: After the failure of multi-line treatment, patients with metastatic thymic tumors have a poor prognosis and few therapeutic options. Combining stereotactic body radiotherapy (SBRT) with granulocyte-macrophage colony-stimulating factor (GM-CSF) and Pegylated interferon-α (Peg-IFNα) may induce abscopal effects and improve prognosis. Methods: We conducted this open-label, single-arm, phase Ⅱ trial to evaluate SBRT plus GM-CSF and Peg-IFNα in previously treated patients with metastatic thymic tumors. A 21-day treatment cycle consisted of SBRT delivered to one metastatic lesion with 30 Gy in 5 fractions from day 1, synchronous subcutaneous injection of GM-CSF 125 μg/ m 2 once daily for 14 days, and subcutaneous injection of Peg-IFNα 90 μg on day 8. If the patient has more than two metastatic lesions, another treatment cycle was repeated. After the completion of 1 or 2 treatment cycles, Peg-IFNα therapy was maintained for at least half a year with a subcutaneous injection of 90 μg once a month. The two primary endpoints were the proportion of patients with abscopal effects and the objective response rate (ORR). The secondary endpoints included overall survival (OS), progression-free survival (PFS), and therapeutic safety. Results: A total of 32 patients from March 2021 to December 2025, were enrolled in this trial, with 2 (6.25%) type A thymoma, 4 (12.50%) type B1 thymoma, 6 (18.75%) type B2 thymoma, 2 (6.25%) type B3 thymoma, 16 (50.00%) thymic squamous cell carcinoma and 2 (6.25%) thymic neuroendocrine tumor. One patient with type B3 thymoma died of cardiac arrest amid the COVID-19 pandemic, rendering tumor evaluation unfeasible. Out of the remaining 31 patients, 9 (29.03%) had abscopal effects, and the ORR was 38.71%. At a median follow-up of 17.20 months, the median OS had not been attained yet. The median PFS was 6.37 months for the whole group. We observed that patients with abscopal effects tended to have longer PFS than those without abscopal effects (13.03 vs. 4.40 months； p = 0.003). 5 patients (16.13%) experienced Grade 3 treatment-related adverse events (CTCAE version 5.0), among which cardiac insufficiency compelled 1 patient (3.23%) to drop out of treatment. Conclusions: Combining SBRT with GM-CSF and Peg-IFNα was well tolerated with acceptable toxicity and may represent a promising salvage therapy for previously treated patients with metastatic thymic tumors. The occurrence of abscopal effects is likely to improve patient outcomes. Clinical trial information: NCT04517539 .