A pilot study combining primary busulfan-based haploidentical stem cell transplantation with GD2 antibody to treat high-risk neuroblastoma

Abstract Very high-risk neuroblastoma is induction-refractory and often harbors mutations in RAS and/or p53 signaling combined with telomere maintenance mechanisms. Event-free survival is <20% in these children. Patients unable to mobilize sufficient hematopoietic stem cells to harvest for busulfan/melphalan-based high-dose chemotherapy before autologous transplantation are also at high risk for relapse. Haploidentical stem cell transplantation (haplo-SCT), offering graft-versus-tumor effects and enhanced antibody-dependent cellular cytotoxicity, has emerged as a feasible treatment. We report administration of a conditioning regimen combining myeloablative busulfan/melphalan anti-tumor therapy with the immunological advantages of haplo-SCT and GD2-directed antibody-based immunotherapy with dinutuximab beta (DB). A 5-patient pilot cohort was treated with systemic induction (salvage) therapy and local therapy per national guidelines. Prior to busulfan, melphalan, fludarabine and antithymocyte globulin conditioning followed by T/B-cell-depleted haplo-SCT and 6 DB cycles, 2 patients received [ 131 I]MIBG therapy. All patients were successfully engrafted. Three of five patients are alive and have remained in first complete remission for 7.3, 6.3 and 1.5 years after haplo-SCT, while two patients experienced events (one relapse, one non-relapse death). Primary busulfan-based haplo-SCT combined with DB immunotherapy was feasible and effective. Early results suggest a survival benefit for these pediatric patient subgroups at very high risk. Confirmation in a larger controlled trial is warranted.