Case Report: Dual Checkpoint Inhibition in Advanced Metastatic Osteosarcoma Results in Remission of All Tumor Manifestations—A Report of a Stunning Success in a 37-Year-Old Patient

Abstract

BackgroundPatients with unresectable metastasized osteosarcoma have a poor prognosis. Current treatment options do not offer a chance to cure the disease in this situation. Despite the fact that immunotherapy has expanded its indications continuously over previous years, its use is not yet established in osteosarcoma. There is a lack of randomized controlled studies that could show a significant benefit in this rare tumor entity. So far, efficacy of immunotherapy is only reported in individual cases as well as in mouse models. To predict a response to immunotherapy, testing for programmed death-ligand 1 (PD-L1) expression, microsatellite instability (MSI), and tumor mutational burden (TMB) can be useful, but status is not yet clear for most cancer entities.MethodsSingle case study and review of the literature.Case PresentationThis report presents the case of a 37-year-old patient with metastatic advanced osteosarcoma, who had no more established options for tumor treatment left. PD-L1 expression in the most recent tumor sample was high (tumor proportion score (TPS) 90%, combined positive score (CPS) 92%) but no MSI could be detected. In an individual therapy attempt, an ongoing and profound remission of all tumor manifestations due to four cycles of immunotherapy with ipilimumab and nivolumab was reached. Despite discontinuation of immunotherapy for 3 months due to therapy-related pneumonitis, remission of all tumor manifestations was ongoing, and no detectable relapse in restaging before onset of Nivolumab-maintenance could be observed.ConclusionThe present case constitutes the first report of an adult patient with metastasized advanced osteosarcoma who reached a deep remission of disease by immunotherapy with ipilimumab and nivolumab, which continued even though immunotherapy had to be interrupted. To verify whether the high expression of PD-L1, as seen in this patient, is a predictive marker for response to immunotherapy in osteosarcoma, requires further investigation.

Anti-PD-1 Therapy in Advanced Pediatric Malignancies in Nationwide Study: Good Outcome in Skin Melanoma and Hodgkin Lymphoma

“…The use of ICIs as a last-chance treatment in our patients with other advanced cancers (Table 4) was usually supported by single case reports or studies on small groups of patients in which this type of treatment proved effective [23][24][25][26][27][28][29][30][31][32][33]. We acknowledge several limitations in our study, including the retrospective nature of the study, the diversity of the types of diseases, and the age of the patients in the cohort group.…”

Osteosarcoma of the Larynx: A Case Report and Review of Literature

“…However, in most of these trials, the drugs used showed little to no improvement in prognosis or the therapeutic effect was not observed [ 8 ]. There is, however, documented success in one instance of advanced metastatic osteosarcoma with nivolumab [ 9 ]. Chimeric antigen receptor T-cell (CAR-T) therapy has shown great promise in treating leukemias and lymphomas and may be a viable option for osteosarcomas.…”

Promise and Challenges of T Cell Immunotherapy for Osteosarcoma

“…A combination of nivolumab and ipilimumab failed to show efficacy in patients with osteosarcoma [46], and a combination of durvalumab (anti-PD-1) and tremelimumab (anti-CTLA4) resulted in two partial responses out of five osteosarcoma patients treated [47]. Several cases reported that the combination of anti-CTLA4 and anti-PD-1 antibodies induced remission and tumor stabilization in patients with metastatic osteosarcoma [48,49], while the addition of camrelizumab (anti-PD-1 inhibitor) to the inhibition of vascular endothelial growth factor receptor 2 (VEGFR2)] using apatinib (tyrosine kinase inhibitor (TKI)) was shown to prolong PFS of patients with advanced osteosarcoma compared with apatinib alone [50]. The overall findings suggest that a combination strategy rather than a stand-alone therapy may be the path to the future.…”