Abstract
Background The pathological subtype of osteosarcoma is one of the most common malignant bone tumors. Notably, chemotherapy-resistant metastatic osteosarcoma has been reported to cause significant mortality and shows poor prognosis with the currently available multidisciplinary treatments. This study investigated whether combined adoptive TIL and anti-PD1 therapy improves the prognosis of patients with chemotherapy-resistant metastatic osteosarcoma. Methods A total of 60 patients with chemotherapy-resistant metastatic osteosarcoma between June 2016 and March 2018 were enrolled. The primary endpoint was to evaluate the safety and adverse effects (AEs) of infusions of TIL and anti-PD1 therapy in the patients. Besides, secondary endpoints included assessing the objective response rate (ORR), progression-free survival time (PFS), and overall survival time (OS). Results We reported that combined TIL therapy and anti-PD1 therapy is safe and all treatment-related AEs were reversible or manageable. The ORR of all the patients is 36.67%, and patients with more infusions of TIL and CD8+TIL, less infusions of CD8+PD1+TIL, and less infusion of CD4+FoxP3+TIL exhibited increased PFS and OS. Conclusion This study determined that combined TIL and anti-PD1 therapy is safe and effective in metastatic osteosarcoma patients with chemotherapy resistance.
Highlights
Osteosarcoma is mortal cancer predominantly affecting children and young adults with a peak age of about 20 years [1]
Between June 2016 and March 2018, 60 patients with chemotherapy-resistant metastatic osteosarcoma were enrolled in this study, and they were treated with tumor-infiltrating lymphocytes (TILs) and nivolumab therapy
Many studies have been conducted on the use of anti-PD1 against osteosarcoma; the objective response rate (ORR) of nonselective patients is less than 10% which significantly lowers the effectiveness of anti-PD1 therapy to osteosarcoma [11]
Summary
Osteosarcoma is mortal cancer predominantly affecting children and young adults with a peak age of about 20 years [1]. 70% of patients with nonmetastatic osteosarcoma can survive for a long time when subjected to the currently developed multidisciplinary treatments [2, 3]. Chemotherapy is the main treatment method for these patients either with or without surgery; it is not effective against metastatic osteosarcoma with 5-year overall survival time (OS) less than 20% [2, 3]. New therapeutic strategies for metastatic osteosarcoma, for patients exhibiting chemotherapy resistance, are urgently needed to improve the prognosis. Chemotherapy-resistant metastatic osteosarcoma has been reported to cause significant mortality and shows poor prognosis with the currently available multidisciplinary treatments. This study investigated whether combined adoptive TIL and anti-PD1 therapy improves the prognosis of patients with chemotherapy-resistant metastatic osteosarcoma. This study determined that combined TIL and anti-PD1 therapy is safe and effective in metastatic osteosarcoma patients with chemotherapy resistance
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