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Article Open Access

Extended cycles of anti‑GD2 antibody dinutuximab beta treatment combined with chemotherapy in patients with relapsed or refractory neuroblastoma: A retrospective study

  • Authors:
    • Zhiqi Gong
    • Suyi Kang
    • Chuanfeng Bai
    • Yang Li
    • Xuedi Yu
    • Kun Shang
    • Yixiang Song
    • Fangfang Cheng
    • Jingfu Wang
  • View Affiliations / Copyright

    Affiliations: Department of Pediatric Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250000, P.R. China
    Copyright: © Gong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 85
    |
    Published online on: December 23, 2025
       https://doi.org/10.3892/ol.2025.15438
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Abstract

Relapsed or refractory high‑risk neuroblastoma (R/R HR‑NB) is associated with a poor prognosis. Although 5 cycles of anti‑GD2 immunotherapy with dinutuximab beta show efficacy, the regimen needs optimization. The present study evaluated the use of extended dinutuximab beta immunotherapy combined with chemotherapy in pediatric patients with R/R NB. In this single‑center retrospective study, children with a median age 5.1 years (range, 2.0‑11.1 years) with R/R HR‑NB who were treated with >5 cycles of dinutuximab beta (10 mg/m²/day for 10‑days per 35‑day cycle), granulocyte‑macrophage colony‑stimulating factor (GM‑CSF) and isotretinoin, plus chemotherapy, were included. The primary outcome of the study was objective response rate (ORR). Secondary outcomes included disease control rate, progression‑free survival (PFS), overall survival (OS) and safety. A total of 30 patients (24 refractory and 6 relapsed) received dinutuximab beta immunotherapy for a median of 7 cycles (range, 6‑12 cycles). Patients with residual disease showed the best ORR of 65%. ORR and complete response (CR) rates improved from 40 and 20%, respectively, at cycle 5/6, to 55 and 30%, respectively, with extended therapy. Notably, 38.5% of patients achieved the best response during cycles beyond the standard 5 cycles. The CR maintenance rate was 90% of patients without residual disease. The 2‑year PFS and OS rate were 83.2 and 94.7%, respectively, with higher outcomes in CR patients (2‑year PFS rate, 90.0%; 2‑year OS rate, 100.0%). Commonly observed grade ≥3 adverse events during the extended phase included infections (90%), neutropenia (86.7%), leukopenia (63.3%) and pain (53.3%), and were generally manageable. No immune‑related deaths occurred. Overall, cycles beyond the standard 5 cycles of dinutuximab beta with chemoimmunotherapy were effective and tolerable in pediatric patients with R/R HR‑NB, demonstrating improved response and survival outcomes. 
View Figures

Figure 1

Treatment regimens and dosing
schedules of chemoimmunotherapy used in relapsed or refractory
neuroblastoma. The VIT regimen consisted of 1.5 mg/m2
vincristine on day 1, 50 mg/m2 irinotecan on days 1–5
and 100 mg/m2 temozolomide on days 1–5. The
platinum-based regimens included DE (20 mg/m2 cisplatin
on days 1–4 and 100 mg/m2 etoposide on days 1–4), OPET
(1.5 mg/m2 vincristine on day 1, 25 mg/m2
cisplatin on days 1–3, 100 mg/m2 etoposide on days 1–3
and 100 mg/m2 temozolomide on days 1–3) or OPEC (1.5
mg/m2 vincristine on day 1, 25 mg/m2
cisplatin on days 1–3, 100 mg/m2 etoposide on days 1–3
and 400 mg/m2 cyclophosphamide on days 1–3). LTI,
long-term infusion; GM-CSF, granulocyte-macrophage
colony-stimulating factor; p.o., oral; Bid, twice a day.

Figure 2

Waterfall plot depicting individual
patient responses to treatment. Different colors indicate the tumor
status at the last follow-up, CR, complete response; PR, partial
response; SD, stable disease; PD, progressive disease.

Figure 3

Assessment of immunotherapeutic
efficacy based on PET-NOTATATE uptake activity. (A) Patient no. 5:
A gradual reduction in SUVmax of bone metastases was observed
following successive cycles of dinutuximab beta immunotherapy. (B)
Patient no. 13: Decreased SUVmax values were noted across multiple
metastatic sites with continued dinutuximab beta treatment,
indicating treatment response. SUVmax, maximum standardized uptake
value; PET/CT, positron emission tomography/computed
tomography.

Figure 4

Kaplan-Meier survival analysis in
patients with relapsed or refractory neuroblastoma. (A) PFS in all
30 patients. (B) OS in all 30 patients. (C) PFS stratified by CR
vs. non-CR status prior to initiation of immunotherapy. (D) OS
stratified by CR vs. non-CR status prior to initiation of
immunotherapy. CR, complete response; PFS, progression-free
survival, OS, overall survival.

Figure 5

Mean duration of morphine use per
treatment cycle in patients with relapsed or refractory
neuroblastoma.
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Copy and paste a formatted citation
Spandidos Publications style
Gong Z, Kang S, Bai C, Li Y, Yu X, Shang K, Song Y, Cheng F and Wang J: Extended cycles of anti‑GD2 antibody dinutuximab beta treatment combined with chemotherapy in patients with relapsed or refractory neuroblastoma: A retrospective study. Oncol Lett 31: 85, 2026.
APA
Gong, Z., Kang, S., Bai, C., Li, Y., Yu, X., Shang, K. ... Wang, J. (2026). Extended cycles of anti‑GD2 antibody dinutuximab beta treatment combined with chemotherapy in patients with relapsed or refractory neuroblastoma: A retrospective study. Oncology Letters, 31, 85. https://doi.org/10.3892/ol.2025.15438
MLA
Gong, Z., Kang, S., Bai, C., Li, Y., Yu, X., Shang, K., Song, Y., Cheng, F., Wang, J."Extended cycles of anti‑GD2 antibody dinutuximab beta treatment combined with chemotherapy in patients with relapsed or refractory neuroblastoma: A retrospective study". Oncology Letters 31.2 (2026): 85.
Chicago
Gong, Z., Kang, S., Bai, C., Li, Y., Yu, X., Shang, K., Song, Y., Cheng, F., Wang, J."Extended cycles of anti‑GD2 antibody dinutuximab beta treatment combined with chemotherapy in patients with relapsed or refractory neuroblastoma: A retrospective study". Oncology Letters 31, no. 2 (2026): 85. https://doi.org/10.3892/ol.2025.15438
Copy and paste a formatted citation
x
Spandidos Publications style
Gong Z, Kang S, Bai C, Li Y, Yu X, Shang K, Song Y, Cheng F and Wang J: Extended cycles of anti‑GD2 antibody dinutuximab beta treatment combined with chemotherapy in patients with relapsed or refractory neuroblastoma: A retrospective study. Oncol Lett 31: 85, 2026.
APA
Gong, Z., Kang, S., Bai, C., Li, Y., Yu, X., Shang, K. ... Wang, J. (2026). Extended cycles of anti‑GD2 antibody dinutuximab beta treatment combined with chemotherapy in patients with relapsed or refractory neuroblastoma: A retrospective study. Oncology Letters, 31, 85. https://doi.org/10.3892/ol.2025.15438
MLA
Gong, Z., Kang, S., Bai, C., Li, Y., Yu, X., Shang, K., Song, Y., Cheng, F., Wang, J."Extended cycles of anti‑GD2 antibody dinutuximab beta treatment combined with chemotherapy in patients with relapsed or refractory neuroblastoma: A retrospective study". Oncology Letters 31.2 (2026): 85.
Chicago
Gong, Z., Kang, S., Bai, C., Li, Y., Yu, X., Shang, K., Song, Y., Cheng, F., Wang, J."Extended cycles of anti‑GD2 antibody dinutuximab beta treatment combined with chemotherapy in patients with relapsed or refractory neuroblastoma: A retrospective study". Oncology Letters 31, no. 2 (2026): 85. https://doi.org/10.3892/ol.2025.15438
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