Results of chemoimmunotherapy for refractory/recurrent GD2-positive bone and soft tissue sarcomas in children. Two centers first experience
S. A. Kulyova,
S. R. Varfolomeeva,
K. I. Kirgizov,
E. A. Prosekina,
O. M. Romantsova,
G. A. Sakhautdinov,
K. M. Borokshinova,
Yu. K. Semenova,
T. V. Gorbunova,
R. I. Khabarova,
E. M. Senchurov,
D. B. Khestanov,
E. D. Gumbatova,
E. A. Mikhailova,
V. V. Khairullova,
M. M. Efimova,
N. V. Matinyan https://doi.org/10.21682/2311-1267-2024-11-4-11-19
Abstract
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.
About the Authors
S. A. Kulyova
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia; Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia
Russian Federation
Russian Federation
Dr. of Sci. (Med.), Professor, Head of Pediatric Oncology Department, Leading Researcher of the Research Department of Innovative Therapeutic Oncology and Rehabilitation Methods, Professor of the Training and Methodology Department; Head of the Department of Oncology, Pediatric Oncology and Radiation Therapy
68 Leningradskaya St., Pesochny, Saint Petersburg, 197758
2 Litovskaya St., Saint Petersburg, 194100
S. R. Varfolomeeva
N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia
Russian Federation
Russian Federation
Dr. of Sci. (Med.), Professor, Director of the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov
23 Kashirskoe Shosse, Moscow, 115522
K. I. Kirgizov
N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia
Russian Federation
Russian Federation
Cand. of Sci. (Med.), Deputy Director for Scientific Work of Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov
23 Kashirskoe Shosse, Moscow, 115522
E. A. Prosekina
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
Russian Federation
Biologist Pathology Department with a Prosector
68 Leningradskaya St., Pesochny, Saint Petersburg, 197758
O. M. Romantsova
N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia
Russian Federation
Russian Federation
Pediatric Oncologist, Head of the Department No. 2 (Chemotherapy of Tumors of the Musculoskeletal System) of the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov
23 Kashirskoe Shosse, Moscow, 115522
G. A. Sakhautdinov
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia; Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia
Russian Federation
Russian Federation
Pediatric Oncologist Pediatric Oncology Department; Assistant, Graduate Student Department of Oncology, Pediatric Oncology and Radiation Therapy
68 Leningradskaya St., Pesochny, Saint Petersburg, 197758
2 Litovskaya St., Saint Petersburg, 194100
K. M. Borokshinova
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
Russian Federation
Pediatric Oncologist Pediatric Oncology Department
68 Leningradskaya St., Pesochny, Saint Petersburg, 197758
Yu. K. Semenova
Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia
Russian Federation
Russian Federation
Graduate Student Department of Biochemistry
2 Litovskaya St., Saint Petersburg, 194100
T. V. Gorbunova
N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia
Russian Federation
Russian Federation
Cand. of Sci. (Med.), Deputy Chief Physician for Medical Affairs and Senior Researcher Childrenʼs Oncology Department of Surgical Treatment Methods with Chemotherapy No. 1 (Head and Neck Tumors) of the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov
23 Kashirskoe Shosse, Moscow, 115522
R. I. Khabarova
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia; Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia
Russian Federation
Russian Federation
Cand. of Sci. (Med.), Pediatric Oncologist Pediatric Oncology Department of the N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia, Assistant Department of Oncology, Pediatric Oncology and Radiation Therapy
68 Leningradskaya St., Pesochny, Saint Petersburg, 197758
2 Litovskaya St., Saint Petersburg, 194100
E. M. Senchurov
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia; Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia
Russian Federation
Russian Federation
Pediatric Oncologist Pediatric Oncology Department of the N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia, Assistant Department of Oncology, Pediatric Oncology and Radiation Therapy
68 Leningradskaya St., Pesochny, Saint Petersburg, 197758
2 Litovskaya St., Saint Petersburg, 194100
D. B. Khestanov
N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia
Russian Federation
Russian Federation
Cand. of Sci. (Med.), Senior Researcher of the Pediatric Oncology Department No. 2 (Chemotherapy of Tumors of the Musculoskeletal System) of the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences
L.A. Durnov
23 Kashirskoe Shosse, Moscow, 115522
E. D. Gumbatova
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
Russian Federation
Cand. of Sci. (Med.), Pediatric Oncologist Pediatric Oncology Department
68 Leningradskaya St., Pesochny, Saint Petersburg, 197758
E. A. Mikhailova
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
Russian Federation
Pediatric Oncologist of the Children Oncology Department, Postgraduate Student of the Research Department of Innovative Therapeutic Oncology and Rehabilitation Methods
68 Leningradskaya St., Pesochny, Saint Petersburg, 197758
V. V. Khairullova
N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia
Russian Federation
Russian Federation
Pediatric Oncologist Pediatric Oncology Department No. 2 (Chemotherapy of Tumors of the Musculoskeletal System) of the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov
23 Kashirskoe Shosse, Moscow, 115522
M. M. Efimova
N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia
Russian Federation
Russian Federation
Pediatric Oncologist Pediatric Oncology Department No. 2 (Chemotherapy of Tumors of the Musculoskeletal System) of the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov
23 Kashirskoe Shosse, Moscow, 115522
N. V. Matinyan
N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia
Russian Federation
Russian Federation
Dr. of Sci. (Med.), Head of the Department of Anesthesiology and Resuscitation of the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov
23 Kashirskoe Shosse, Moscow, 115522
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For citations:
Kulyova S.A., Varfolomeeva S.R., Kirgizov K.I., Prosekina E.A., Romantsova O.M., Sakhautdinov G.A., Borokshinova K.M., Semenova Yu.K., Gorbunova T.V., Khabarova R.I., Senchurov E.M., Khestanov D.B., Gumbatova E.D., Mikhailova E.A., Khairullova V.V., Efimova M.M., Matinyan N.V. Results of chemoimmunotherapy for refractory/recurrent GD2-positive bone and soft tissue sarcomas in children. Two centers first experience. Russian Journal of Pediatric Hematology and Oncology. 2024;11(4):11-19. (In Russ.) https://doi.org/10.21682/2311-1267-2024-11-4-11-19
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