PO-04. Dinutuximab beta immunotherapy after autologous and allogeneic hemopoietic stem cell transplantation in patients with high- and ultrahigh-risk group neuroblastoma: RM Gorbacheva Research Institute experience
Ilya V. Kazantsev, Asmik G. Gevorgian, Polina S. Tolkunova, Tatiana V. Iukhta, Daria A. Drozdovskaya, Andrew V. Kozlov, Margarita S. Golenkova, Alexander N. Galimov, Olga I. Bogdanova, Ekaterina V. Goncharova, Yuri A. Punanov, Alexander D. Kulagin, Ludmila S. Zubarovskaya
RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia
Dr. Ilya V. Kazantsev, phone +7 (963) 348-05-24, e-mail: Ilya_Kazantsev@inbox.ru
Neuroblastoma (NB) is the most common extracranial solid tumor in infants and younger children characterized by significant biological and clinical heterogeneity. The currently used Russian standard of treatment for high-risk patients allows achieving the long-term survival of about 40% in spite of highly intensive complex therapy used. In ultrahigh-risk group the results are even worse with less than 10% of patients achieving a durable response. Also, there is still no consensus on optimal treatment of patients with primary resistant disease or relapse and the prognosis in this cohort is still dismal. Immunotherapy with anti-GD2 antibodies is potentially effective in these situations. It may also be used in autologous (auto-HSCT) or haploidentical donor allogeneic stem cell transplantation (haplo-HSCT) settings.
Patients and methods
In 2017-2021 a total of 19 patients with NB received 76 courses of anti-GD2 antibodies (dinutuximab beta) immunotherapy after auto-HSCT (n=13) and allo-HSCT (n=6) within two pilot trials conducted by RM Gorbacheva Research Institute. All auto-HSCT recipients belonged to high-risk group and previously achieved complete or very good partial response, 3 of them belonged to ultrahigh-risk group according to stratification scale by Morgentern DA et al. The haplo-HSCT recipients were treated for primary resistant-disease (n=1), first (n=4) or second (n=1) systemic relapse. In all cases prior to haplo-HSCT a non-myeloablative (Flu-Mel) conditioning regimen was used. In 5 of 6 cases the graft-versus-host disease (GVHD) prophylaxis was post-transplant cyclophosphamide based. In 4 of 6 cases patients retained a complete or very good partial response at the time of immunotherapy initiation. In 2 cases patients received immunotherapy due to early relapse post haplo-HSCT. In both cases immunotherapy was given in combination with temozolomide.
With a median follow-up of 16 (6-27) months 11 of 13 patients receiving immunotherapy after auto-HSCT retain complete response. Two patients, both from ultrahigh-risk subgroup relapsed, bub responded well to salvage therapy. Therefore, the EFS and OS in this group are currently 80% and 100%, accordingly. The patients with 1st and 2nd relapse are still in remission 17, 37 and 43 months after haplo-HSCT. The patent with primary resistant disease relapsed in 55 months. Both patients receiving immunotherapy as salvage treatment died of disease progression with no signs of response. The overall anti-GD2 immunotherapy toxicity was acceptable. No signs of clinically significant GVHD were observed in haplo-HSCT recipients. There were, however, 4 cases of neurotoxicity (2 in auto- and 2 in haplo-HSCT recipients), requiring therapy cessation in 2 cases.
Dinutuximab beta immunotherapy is characterized by acceptable toxicity both in auto- and haplo-HSCT recipients. It allows achieving good short-term results, although these results are much worse in patients with chemoresistant disease of ultrahigh-risk group patients. The larger cohort and longer follow-up are needed to clearly evaluate long-term results.
Neuroblastoma, high-risk group, ultrahigh-risk group, immunotherapy, auto-HSCT, haplo-HSCT.