In a phase I/II trial reported in the Journal of Clinical Oncology, Flaadt et al found that treatment with the anti-GD2 antibody dinutuximab beta plus low-dose interleukin-2 (IL-2) following haploidentical stem cell transplantation (haplo-SCT) is feasible in patients with relapsed high-risk neuroblastoma. The treatment had a low risk of inducing graft-vs-host disease and led to long-term remission in some patients.
As stated by the investigators, “Patients with relapsed high-risk neuroblastoma have a poor prognosis. We hypothesized that graft-vs-neuroblastoma effects could be elicited by transplantation of haploidentical stem cells exploiting cytotoxic functions of natural killer cells and their activation by the anti-GD2 antibody dinutuximab beta.”
In the study, 68 patients aged 1 to 21 years enrolled between November 2010 and November 2017 at four European centers. Patients underwent T-cell/B-cell–depleted haplo-SCT from haploidentical siblings followed by treatment with dinutuximab beta and subcutaneous low-dose IL-2. Dinutuximab beta was given at 20 mg/m2 once per day on 5 consecutive days in a total of six cycles given every 4 weeks. IL-2 at 1 × 106 IU/m2 was added in cycles four to six on days 6, 8, 10.
The primary endpoint was defined as patients’ receiving six cycles; being alive 180 days after the end of trial treatment; and having no progressive disease, unacceptable toxicity, acute ≥ 3 graft-vs-host-disease, or extensive chronic graft-vs-host-disease.
The primary endpoint was met by 37 (54.4%) of 68 patients. Median follow-up was 7.8 years. Five-year event-free survival and overall survival from the start of study treatment were 43% (95% confidence interval [CI] = 31%–55%) and 53% (95% CI = 41%–65%), respectively.
Five-year event-free survival among patients with complete remission (52%, 95% CI = 31%–69%) or partial remission (44%, 95% CI = 27%–60%) before immunotherapy were significantly improved (overall P = .26) vs patients with nonresponse, mixed response, or progressive disease (13%, 95% CI = 1%–42%). Similar outcomes were observed for overall survival (overall P = .001).
The cumulative incidence of relapse or disease progression at 5 years was 49% (95% CI = 37%–61%). Among 43 patients with evidence of disease after haplo-SCT, complete or partial remission was achieved in 22 (51%), with complete remission in 15 (35%).
Hematologic grade 3 or 4 adverse events occurred in 42.6% of patients. The majority of nonhematologic grade 3 or 4 adverse events were fever, pain, hypersensitivity reactions, capillary leak syndrome, elevated liver enzymes, and central neurotoxicity. Late-onset acute graft-vs-host-disease during dinutuximab beta treatment occurred in five patients (7.4%): two patients developed grade 2 and 3 acute graft-vs-host-disease of the gut, and three developed grade 1/2 skin graft-vs-host-disease.
The investigators concluded, “Dinutuximab beta therapy after haplo-SCT in patients with relapsed high-risk neuroblastoma is feasible, with low risk of inducing graft-vs-host-disease, and results in long-term remissions likely attributable to increased antineuroblastoma activity by donor-derived effector cells.”
Tim Flaadt, MD, of the Department of Hematology and Oncology, University Children’s Hospital, Eberhard Karls University Tuebingen, Germany, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Aktion Nils, Gesellschaft fuer Kinderkrebsforschung Geltendorf, and others. For full disclosures of the study authors, visit ascopubs.org.