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
Standard
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. / Flaadt, Tim; Ladenstein, Ruth L; Ebinger, Martin; Lode, Holger N; Arnardóttir, Helga Björk; Poetschger, Ulrike; Schwinger, Wolfgang; Meisel, Roland; Schuster, Friedhelm R; Döring, Michaela; Ambros, Peter F; Queudeville, Manon; Fuchs, Jörg; Warmann, Steven W; Schäfer, Jürgen; Seitz, Christian; Schlegel, Patrick; Brecht, Ines B; Holzer, Ursula; Feuchtinger, Tobias; Simon, Thorsten; Schulte, Johannes H; Eggert, Angelika; Teltschik, Heiko-Manuel; Illhardt, Toni; Handgretinger, Rupert; Lang, Peter.
In: J CLIN ONCOL, Vol. 41, No. 17, 10.06.2023, p. 3135-3148.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - 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
AU - Flaadt, Tim
AU - Ladenstein, Ruth L
AU - Ebinger, Martin
AU - Lode, Holger N
AU - Arnardóttir, Helga Björk
AU - Poetschger, Ulrike
AU - Schwinger, Wolfgang
AU - Meisel, Roland
AU - Schuster, Friedhelm R
AU - Döring, Michaela
AU - Ambros, Peter F
AU - Queudeville, Manon
AU - Fuchs, Jörg
AU - Warmann, Steven W
AU - Schäfer, Jürgen
AU - Seitz, Christian
AU - Schlegel, Patrick
AU - Brecht, Ines B
AU - Holzer, Ursula
AU - Feuchtinger, Tobias
AU - Simon, Thorsten
AU - Schulte, Johannes H
AU - Eggert, Angelika
AU - Teltschik, Heiko-Manuel
AU - Illhardt, Toni
AU - Handgretinger, Rupert
AU - Lang, Peter
PY - 2023/6/10
Y1 - 2023/6/10
N2 - 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.
AB - 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.
KW - Humans
KW - Infant
KW - Child, Preschool
KW - Child
KW - Adolescent
KW - Young Adult
KW - Adult
KW - Interleukin-2/therapeutic use
KW - Neoplasm Recurrence, Local/therapy
KW - Neuroblastoma/drug therapy
KW - Hematopoietic Stem Cell Transplantation/adverse effects
KW - Graft vs Host Disease/etiology
U2 - 10.1200/JCO.22.01630
DO - 10.1200/JCO.22.01630
M3 - SCORING: Journal article
C2 - 36854071
VL - 41
SP - 3135
EP - 3148
JO - J CLIN ONCOL
JF - J CLIN ONCOL
SN - 0732-183X
IS - 17
ER -