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. 2025 Jan 5;17(1):149.
doi: 10.3390/cancers17010149.

Long-Term Outcomes and Quality of Life of High-Risk Neuroblastoma Patients Treated with a Multimodal Treatment Including Anti-GD2 Immunotherapy: A Retrospective Cohort Study

Tim Flaadt  1 , Jonas Rehm  1 , Thorsten Simon  2 , Barbara Hero  2 , Ruth L Ladenstein  3 , Holger N Lode  4 , Desiree Grabow  5 , Sandra Nolte  6   7 , Roman Crazzolara  8 , Johann Greil  9 , Martin Ebinger  1 , Michael Abele  1 , Ursula Holzer  1 , Michaela Döring  1 , Johannes H Schulte  1 , Peter Bader  10 , Paul-Gerhardt Schlegel  11 , Matthias Eyrich  11 , Peter Lang  1 , Thomas Klingebiel  10 , Rupert Handgretinger  1
Affiliations

Long-Term Outcomes and Quality of Life of High-Risk Neuroblastoma Patients Treated with a Multimodal Treatment Including Anti-GD2 Immunotherapy: A Retrospective Cohort Study

Tim Flaadt et al. Cancers (Basel). .

Abstract

Background: The incorporation of anti-GD2 antibodies such as ch14.18/SP2/0 into the multimodal treatment of high-risk neuroblastoma (HR-NB) patients has improved their outcomes. As studies assessing the long-term outcomes, long-term sequelae, and health-related quality of life (HRQoL) of this treatment are limited, this retrospective analysis aimed to explore these.

Patients and methods: Between 1991 and 2002, 65 children received a multimodal treatment, including ch14.18/SP2/0, for primary HR-NB. All received chemotherapy according to the NB90/NB97 trial, 51 received high-dose chemotherapy, and all received ch14.18/SP2/0 treatment. We analyzed the long-term sequelae and HRQoL (EORTC QLQ-C30), and evaluated overall and event-free survival (OS/EFS).

Results: Twenty-five survivors were evaluated for HRQoL and long-term effects. All reported long-term sequelae, including ototoxicity in 16/25 (64%), cardiac toxicity in 6/25 (24%), and endocrine toxicity in 19/25 (76%) patients. Chronic diarrhea was reported in 20% of female patients. Seven patients developed autoimmune diseases. HRQoL scores were better across multiple scales than those of the matched German general population. Twenty-five-year OS and EFS were 50.8% (95% confidence interval: 31-55) and 43% (30.1-55.3), with 33 (50.8%) long-term survivors. Thirty-two patients died: 28 (43.1%) because of progression/relapse and 4 (6.2%) because of secondary neoplasms.

Conclusions: Multimodal treatment, including ch14.18/SP2/0, can achieve long-term survival in HR-NB patients, with a substantial proportion of survivors reporting better HRQoL compared to the general population. All patients reported long-term side effects mostly attributable to chemotherapy and radiotherapy. The relatively high prevalence of autoimmune diseases and persistent diarrhea warrants additional longitudinal research on individuals treated with anti-GD2 antibodies.

Keywords: immunotherapy; long-term follow-up; neuroblastoma; pediatric oncology.

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Conflict of interest statement

The authors declare no conflicts of interest and the funders had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
(A) Overview of the therapy: In the NB90 trial, high-dose chemotherapy (HDC) with autologous stem cell transplantation was optional; however, all patients in the present cohort received HDC. The NB97 trial was a prospective randomized trial comparing HDC with oral maintenance therapy consisting of four cycles of oral cyclophosphamide for days 1–8 every 28 days. ASCT: autologous stem cell transplantation. (B) Details of the study population: 25/33 long-term survivors participated in the long-term survey; the remaining 8 patients did not participate for personal reasons. Nevertheless, the follow-up was updated for these patients. HR-NB: high-risk neuroblastoma. NB90: induction therapy according to German NB90 trial. NB97: induction therapy according to the German NB97 trial. mIBG: iodine meta-iodobenzylguanidine. HDC: high-dose chemotherapy. ASCT: autologous stem cell transplantation. ch14.18/SP2/0: treatment with the chimeric anti-GD2 antibody ch.14.18/SP2/0. SMN: secondary malignancy.
Figure 2
Figure 2
Overall survival (A), event-free survival (B), cumulative incidence of relapse (C), and incidence of secondary cancers (D) of the whole cohort.
See this image and copyright information in PMC

References

    1. Maris J.M., Hogarty M.D., Bagatell R., Cohn S.L. Neuroblastoma. Lancet. 2007;369:2106–2120. doi: 10.1016/S0140-6736(07)60983-0. - DOI - PubMed
    1. Matthay K.K., Reynolds C.P., Seeger R.C., Shimada H., Adkins E.S., Haas-Kogan D., Gerbing R.B., London W.B., Villablanca J.G. Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: A children’s oncology group study. J. Clin. Oncol. 2009;27:1007–1013. doi: 10.1200/JCO.2007.13.8925. - DOI - PMC - PubMed
    1. Matthay K.K., Atkinson J.B., Stram D.O., Selch M., Reynolds C.P., Seeger R.C. Patterns of relapse after autologous purged bone marrow transplantation for neuroblastoma: A Childrens Cancer Group pilot study. J. Clin. Oncol. 1993;11:2226–2233. doi: 10.1200/JCO.1993.11.11.2226. - DOI - PubMed
    1. Yu A.L., Gilman A.L., Ozkaynak M.F., London W.B., Kreissman S.G., Chen H.X., Smith M., Anderson B., Villablanca J.G., Matthay K.K., et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N. Engl. J. Med. 2010;363:1324–1334. doi: 10.1056/NEJMoa0911123. - DOI - PMC - PubMed
    1. Yu A.L., Gilman A.L., Ozkaynak M.F., Naranjo A., Diccianni M.B., Gan J., Hank J.A., Batova A., London W.B., Tenney S.C., et al. Long-Term Follow-up of a Phase III Study of ch14.18 (Dinutuximab) + Cytokine Immunotherapy in Children with High-Risk Neuroblastoma: COG Study ANBL0032. Clin. Cancer Res. 2021;27:2179–2189. doi: 10.1158/1078-0432.CCR-20-3909. - DOI - PMC - PubMed

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