Long term outcome of high-risk neuroblastoma patients after immunotherapy with antibody ch14.18 or oral metronomic chemotherapy.
BACKGROUND
The treatment of high-risk neuroblastoma patients consists of multimodal induction therapy to achieve remission followed by consolidation therapy to prevent relapses. However, the type of consolidation therapy is still discussed controversial. We applied metronomic chemotherapy in the prospective NB90 trial and monoclonal anti-GD2-antibody (MAB) ch14.18 in the NB97 trial. Here, we present the long term outcome data of the patient cohort.


METHODS
A total of 334 stage 4 neuroblastoma patients one year or older were included. All patients successfully completed the induction therapy. In the NB90 trial, 99 patients received at least one cycle of the oral maintenance chemotherapy (NB90 MT, 12 alternating cycles of oral melphalan/etoposide and vincristine/cyclophosphamide). In the NB97 trial, 166 patients commenced the MAB ch14.18 consolidation therapy (six cycles over 12 months). Patients who received no maintenance therapy according to the NB90 protocol or by refusal in NB97 (n = 69) served as controls.


RESULTS
The median observation time was 11.11 years. The nine-year event-free survival rates were 41 ± 4%, 31 ± 5%, and 32 ± 6% for MAB ch14.18, NB90 MT, and no consolidation, respectively (p = 0.098). In contrast to earlier reports, MAB ch14.18 treatment improved the long-term outcome compared to no additional therapy (p = 0.038). The overall survival was better in the MAB ch14.18-treated group (9-y-OS 46 ± 4%) compared to NB90 MT (34 ± 5%, p = 0.026) and to no consolidation (35 ± 6%, p = 0.019). Multivariable Cox regression analysis revealed ch14.18 consolidation to improve outcome compared to no consolidation, however, no difference between NB90 MT and MAB ch14.18-treated patients was found.


CONCLUSIONS
Follow-up analysis of the patient cohort indicated that immunotherapy with MAB ch14.18 may prevent late relapses. Finally, metronomic oral maintenance chemotherapy also appeared effective.
Children's Hospital, University of Cologne, Cologne, Germany. thorsten.simon@uk-koeln.de
Thorsten
T
Simon
Barbara
B
Hero
Andreas
A
Faldum
Rupert
R
Handgretinger
Martin
M
Schrappe
Thomas
T
Klingebiel
Frank
F
Berthold
D000284:Administration, Oral; D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004358:Drug Therapy / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007223:Infant; D008297:Male; D015999:Multivariate Analysis; D009447:Neuroblastoma / Q000276:immunology / Q000628:therapy*; D017063:Outcome Assessment, Health Care; D012044:Regression Analysis; D012307:Risk Factors; D033581:Stem Cell Transplantation / Q000379:methods; D013997:Time Factors; D014182:Transplantation, Autologous; D055815:Young Adult
D000911:Antibodies, Monoclonal; C112746:dinutuximab
Lancet Oncol. 2008 Mar;9(3):247-56
18308250
Strahlenther Onkol. 2006 Jul;182(7):389-94
16826357
Eur J Cancer. 1998 Aug;34(9):1398-402
9849423
Cancer Lett. 2003 Jul 18;197(1-2):11-7
12880954
J Clin Oncol. 2000 Dec 15;18(24):4077-85
11118469
J Clin Oncol. 1998 Jun;16(6):2169-80
9626218
J Clin Oncol. 2001 Nov 15;19(22):4189-94
11709561
Klin Padiatr. 2005 May-Jun;217(3):147-52
15858706
Lancet Oncol. 2005 Sep;6(9):649-58
16129365
J Clin Oncol. 1994 Jan;12(1):184-93
8270976
Eur J Cancer. 1995;31A(2):261-7
7718335
Cancer. 1997 Jul 15;80(2):317-33
9217046
Cancer Immunol Immunother. 1992;35(3):199-204
1638557
J Clin Oncol. 2004 Sep 1;22(17):3549-57
15337804
N Engl J Med. 2010 Sep 30;363(14):1324-34
20879881
N Engl J Med. 1999 Oct 14;341(16):1165-73
10519894
J Clin Oncol. 1993 Aug;11(8):1466-77
8336186
Int J Oncol. 1998 Jun;12(6):1299-306
9592190
J Clin Oncol. 2009 Jan 1;27(1):85-91
19047298
J Clin Oncol. 1987 Sep;5(9):1430-40
3625258