Retrospective Analysis of Adoptive TIL Therapy plus Anti-PD1 Therapy in Patients with Chemotherapy-Resistant Metastatic Osteosarcoma

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.

Risk Factors, Prognostic Factors, and Nomograms for Distant Metastasis in Patients With Newly Diagnosed Osteosarcoma: A Population-Based Study

“…Although osteosarcoma patients with DM dramatically develop more lesions and become resistant to chemotherapy (14), underscoring a critical need for new treatments strategies, continuous chemotherapy still plays an important role in prolonging patients' life and several clinical trials are still ongoing (41,42). Surgery alone, the only effective way to treat osteosarcoma decades ago, which consisted of removing the tumor of amputating, didn't reduce mortality below 80%, but there is still a place for osteosarcoma patients with DM (1).…”

“…Approximately 20-30% of osteosarcoma patients presented clinical DM (most commonly in the lung) at the time of the first diagnosis (10,11), and about 25-35% of patients with initially non-metastatic osteosarcoma subsequently develop metastatic diseases (12,13). Of note, osteosarcoma patients with DM promptly develop more lesions and become resistant to chemotherapy (14), with dismal 5-year overall survival (OS) time less than 20% (15). Therefore, it is imperative to construct exact models to assess the risk of DM of osteosarcoma patients and evaluate the prognosis of patients with DM.…”

Adoptive Cellular Therapy for Pediatric Solid Tumors: Beyond Chimeric Antigen Receptor-T Cell Therapy

“…A study of the TARGET database using 27 matched osteosarcoma patient samples assessed changes in the immune environment after chemotherapy and found that neoadjuvant chemotherapy was associated with increased infiltration of all T cells, and specifically CD8 + T cells, into the tumors, with decrease in myeloid-derived suppressive cells 82 . Additional work has found that genomic instability of osteosarcoma leads to neoantigen generation, potentially making it more immunogenic or “hot”; in this study, increased TILs were found in metastatic disease compared with the primary tumor, hinting a use for T-cell–based immunotherapy in metastatic osteosarcoma 83 . Two active trials using TIL therapy along with lymphodepleting chemotherapy and post-TIL IL-2 are currently enrolling patients as young as 16 years old (NCT03449108, NCT04052334).…”

The perplexing role of immuno-oncology drugs in osteosarcoma

“…treated 60 patients with metastatic osteosarcoma previously treated with chemotherapy with nivolumab q2weeks and injected individual patient derived cultured TILs from fresh tumour biopsies. The ORR by response evaluation criteria in solid tumours (RECIST) 1.1 was 36.7% (n = 22/60, 2 complete response (CR) and 20 partial response (PR)), with the median progression free (mPFS) and overall survival (mOS) 5.6 months and 13.6 months respectively for the entire population [53] . Patients with an objective response had a longer mPFS (8.9 months) and mOS (23.7 months).…”