Results of chemoimmunotherapy for refractory/recurrent GD2-positive bone and soft tissue sarcomas in children. Two centers first experience

Background. In the literature, information on the overexpression of disialoganglioside GD2 on the cells of malignant neoplasms is not uncommon. In this regard, this marker should be considered as a tumor-associated antigen, which may be a target on the cell surface in patients with poor prognosis. The aim of the study – improve the efficacy of the treatment of children and adolescents with refractory and recurrent solid malignancies (soft tissue, undifferentiated (unSA) and bone sarcomas) by incorporating targeted immunotherapeutic options (immunotherapy with antiGD2 monoclonal antibodies (MA)) into comprehensive therapy programs. Materials and methods. Ten patients with GD2-positive relapsed/refractory soft tissue sarcomas (STS, n = 4), osteosarcomas (OS, n = 2), Ewingʼs sarcomas (ES, n = 4) and unSA (n = 1) were included in the study. The gender ratio was 2.3:1 (boys:girls). The mean age at the time of inclusion in the study was 12 ± 2 years. The most of all patients (80 %) had a status of “primary resistant disease”. GD2 quantitative expression level was 29 ± 11 % (0.9 to 85 %). Patients were represented by deeply pretreated patients who received 8 to 25 cycles of 2+ line chemotherapy (mean 13). A total of 7 patients completed the full reinduction treatment (6 cycles of chemoimmunotherapy). All patients received anti-GD2 MA 100 mg/m2 as an intravenous 5-day infusion every 4 weeks, and treatment was continued until disease progression or 6 cycles. Fifty-two cycles of immunotherapy were performed. Results. Pain syndrome was the most frequently diagnosed (after 16 cycles, or in 30.7 % of cases); 5 (9.6 %) cycles each were accompanied by diarrhea, cytokine release syndrome, and increased capillary permeability syndrome. The immediate results varied according to the histological subtype of the tumor. The overall objective response rate was 43 % (3/7): 2 patients achieved complete remission (CR) and one achieved partial remission (PR). The disease control rate (CR + PR + stable) was 86 % (6/7). The clinical response rate 6 months after completion of chemoimmunotherapy ranged from 0 % (2/2) in ES to 50 % (1/2) in OS. In 43 % (3/7) of evaluable patients, disease progression was diagnosed after a mean of 5 months. At follow-up after 12 and 24 months, CR persisted in all patients with STS (100 %). Progression-free survival (PFS) in patients with STS at 6, 12 and 24 months was 100 % (PFS6, PFS12, PFS24, respectively). PFS6 in OS and ES patients was 100 % and 50 %, respectively, gradually decreasing to 0 %. The study revealed a very strong positive straight-line positive functional correlation between quantitative GD2 expression and progression-free survival (r = 0.971, p = 0.00006). Conclusion. Passive immunotherapy with monoclonal antibodies is a safe treatment method without severe immune-related adverse reactions. Patient follow-up and evaluation of the efficacy and safety of the drug after the end of the therapy plan continues until today, which allows a more detailed and objective evaluation of the results of immunotherapy according to the purpose of the study.