Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Flaadt, T; Ladenstein, RL; Ebinger, M; Lode, HN; Arnardóttir, HB; Poetschger, U; Schwinger, W; Meisel, R; Schuster, FR; Döring, M; Ambros, PF; Queudeville, M; Fuchs, J; Warmann, SW; Schäfer, J; Seitz, C; Schlegel, P; Brecht, IB; Holzer, U; Feuchtinger, T; Simon, T; Schulte, JH; Eggert, A; Teltschik, HM; Illhardt, T; Handgretinger, R; Lang, P.
Anti-GD2 Antibody Dinutuximab Beta and Low-Dose Interleukin 2 After Haploidentical Stem-Cell Transplantation in Patients With Relapsed Neuroblastoma: A Multicenter, Phase I/II Trial.
J Clin Oncol. 2023; 41(17): 3135-3148.
Doi: 10.1200/JCO.22.01630
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- Co-Autor*innen der Med Uni Graz
- Schwinger Wolfgang
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- Abstract:
- PURPOSE: Patients with relapsed high-risk neuroblastoma (rHR-NB) have a poor prognosis. We hypothesized that graft-versus-neuroblastoma effects could be elicited by transplantation of haploidentical stem cells (haplo-SCT) exploiting cytotoxic functions of natural killer cells and their activation by the anti-GD2 antibody dinutuximab beta (DB). This phase I/II trial assessed safety, feasibility, and outcomes of immunotherapy with DB plus subcutaneous interleukin-2 (scIL2) after haplo-SCT in patients with rHR-NB. METHODS: Patients age 1-21 years underwent T-/B-cell-depleted haplo-SCT followed by DB and scIL2. The primary end point 'success of treatment' encompassed patients receiving six cycles, being alive 180 days after end of trial treatment without progressive disease, unacceptable toxicity, acute graft-versus-host-disease (GvHD) ≥grade 3, or extensive chronic GvHD. RESULTS: Seventy patients were screened, and 68 were eligible for immunotherapy. Median number of DB cycles was 6 (range, 1-9). Median number of scIL2 cycles was 3 (1-6). The primary end point was met by 37 patients (54.4%). Median observation time was 7.8 years. Five-year event-free survival (EFS) and overall survival from start of trial treatment were 43% (95% CI, 31 to 55) and 53% (95% CI, 41 to 65), respectively. Five-year EFS among patients in complete remission (CR; 52%; 95% CI, 31 to 69) or partial remission (44%; 95% CI, 27 to 60) before immunotherapy were significantly better compared with patients with nonresponse/mixed response/progressive disease (13%; 95% CI, 1 to 42; P = .026). Overall response rate in 43 patients with evidence of disease after haplo-SCT was 51% (22 patients), with 15 achieving CR (35%). Two patients developed GvHD grade 2 and 3 each. No unexpected adverse events occurred. CONCLUSION: DB therapy after haplo-SCT in patients with rHR-NB is feasible, with low risk of inducing GvHD, and results in long-term remissions likely attributable to increased antineuroblastoma activity by donor-derived effector cells.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Infant - administration & dosage
- Child, Preschool - administration & dosage
- Child - administration & dosage
- Adolescent - administration & dosage
- Young Adult - administration & dosage
- Adult - administration & dosage
- Interleukin-2 - therapeutic use
- Neoplasm Recurrence, Local - therapy, etiology
- Neuroblastoma - drug therapy
- Hematopoietic Stem Cell Transplantation - adverse effects, methods
- Graft vs Host Disease - etiology