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. 2023 Sep 25;12(19):6196.
doi: 10.3390/jcm12196196.

Multimodal Therapy with Consolidating Haploidentical Stem Cell Transplantation and Dinutuximab Beta for Patients with High-Risk Neuroblastoma and Central Nervous System Relapse

Tim Flaadt  1 , Martin Ebinger  1 , Malin Schreiber  1 , Ruth L Ladenstein  2   3 , Thorsten Simon  4 , Holger N Lode  5 , Barbara Hero  4 , Martin U Schuhmann  6 , Jürgen Schäfer  7 , Frank Paulsen  8 , Beate Timmermann  9 , Angelika Eggert  10 , Peter Lang  1
Affiliations

Multimodal Therapy with Consolidating Haploidentical Stem Cell Transplantation and Dinutuximab Beta for Patients with High-Risk Neuroblastoma and Central Nervous System Relapse

Tim Flaadt et al. J Clin Med. .

Abstract

Despite highly intensive multimodality treatment regimens, the prognosis of patients with high-risk neuroblastoma (HRNB) and central nervous system (CNS) relapse remains poor. We retrospectively reviewed data from 13 patients with HRNB and CNS relapse who received multimodal therapy with consolidating haploidentical stem cell transplantation (haplo-SCT) followed by dinutuximab beta ± subcutaneous interleukin-2 (scIL-2). Following individual relapse treatment, patients aged 1-21 years underwent haplo-SCT with T/B-cell-depleted grafts followed by dinutuximab beta 20 mg/m2/day × 5 days for 5-6 cycles. If a response was demonstrated after cycle 5 or 6, patients received up to nine treatment cycles. After haplo-SCT, eight patients had a complete response, four had a partial response, and one had a stable disease. All 13 patients received ≥3 cycles of immunotherapy. At the end of the follow-up, 9/13 patients (66.7%) demonstrated complete response. As of July 2023, all nine patients remain disease-free, with a median follow-up time of 5.1 years since relapse. Estimated 5-year event-free and overall survival rates were 55.5% and 65.27%, respectively. Dinutuximab beta ± scIL-2 following haplo-SCT is a promising treatment option with a generally well-tolerated safety profile for patients with HRNB and CNS relapse.

Keywords: central nervous system; dinutuximab beta; neuroblastoma; recurrence.

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Conflict of interest statement

T.F. received travel, accommodations, and expenses from EUSA Pharma and has served as a consultant/advisor for EUSA Pharma. M.E. served as a consultant/advisor for Amgen, Boehringer Ingelheim, and Bayer Germany. R.L.L. received honoraria from and served as a consultant/advisor for Apeiron Biologics, Boehringer Ingelheim, and EUSA Pharma. R.L.L. also received research funding, patents, royalties, other intellectual property, expert testimony, travel, accommodations, and expenses from Apeiron Biologics and EUSA Pharma. T.S. served as a consultant/advisor for EUSA Pharma, Norgine Ltd., and Merck. H.N.L. received honoraria, travel, accommodations, and expenses from EUSA Pharma. H.N.L. also served as a consultant/advisor for EUSA Pharma and received research funding from Roche Pharma AG and EUSA Pharma. A.E. served as a consultant/advisor for EUSA Pharma. P.L. received research funding from EUSA Pharma. M.S., B.H., M.U.S., J.S., F.P., and B.T. declare no conflicts of interest.

Figures

Figure 1
Figure 1
Disease status before and after dinutuximab beta treatment. CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease.
Figure 2
Figure 2
Axial view of brain MRI scans from a patient with neuroblastoma (patient 11) showing intracranial left-frontal metastases at (A) initial relapse, (B) after reinduction chemotherapy and radiotherapy, (C) after haplo-SCT, (D) after dinutuximab beta treatment completion, and (E) 18 months after haplo-SCT. Red circles show the site of metastases. Haplo-SCT, haploidentical stem cell transplantation; MRI, magnetic resonance imaging.
Figure 3
Figure 3
Kaplan–Meier curves demonstrating EFS (A) and OS (B) in patients with neuroblastoma and CNS relapse treated with haplo-SCT and dinutuximab beta therapy as part of multimodal therapy. Five-year EFS for the whole cohort (years since CNS relapse): 55.9% (95% CI 78.9–23.9); 5-year OS for the whole cohort (years since CNS relapse): 65.3% (95% CI 85.5–31.5). CNS, central nervous system; CI, confidence interval; EFS, event-free survival; haplo-SCT, haplo-identical stem cell transplantation; OS, overall survival.
See this image and copyright information in PMC

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