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By Lynda Williams, medwireNews Reporter

medwireNews: Children with relapsed, high-risk neuroblastoma may benefit from immunotherapy with dinutuximab beta (DB) after haploidentical stem-cell transplantation (haplo-SCT), investigators write in the Journal of Clinical Oncology.

Tim Flaadt (Eberhard Karls University Tuebingen, Germany) and co-authors say that the combined approach achieved “notable” 5-year event-free survival (EFS) and overall survival (OS) rates of 43% and 53%, respectively, compared with previously reported corresponding rates with haplo-SCT alone of 19% and 23%.

They explain that the use of the anti-GD2 antibody DB may “augment graft-versus-neuroblastoma effects after haplo-SCT through early expanding and persisting donor-derived [natural killer] cells.”

The phase 1–2 trial included 68 patients aged 3–20 years (median 6.5 years) with relapsed or treatment-refractory stage 4 neuroblastoma (94.1%) or relapsed MYCN-amplified stage 2–3 neuroblastoma.

These patients had previously been treated for relapse with chemotherapy (98.5%), surgery (57.4%) or radiation (38.2%), and 63.2% of patients received radioactive iodine-131 mIBG treatment targeted at neuroendocrine cells before undergoing haplo-SCT. A minority (14.7%) of patients had previously received anti-GD2 therapy.

Sixty days after transplantation, patients were given a daily 8-hour infusion of DB 20 mg/m2 for 5 days and this was repeated every 4 weeks, with an initial plan of six cycles and an additional three cycles for responding or stable patients. Low-dose subcutaneous interleukin-2 was given to prevent graft-versus-host disease (GvHD) during cycles 4–6.

The patients received a median six cycles of DB and three cycles of interleukin-2 and were followed up for a median of 7.8 years.

Overall, 54.4% of patients achieved the primary endpoint of survival for 180 days after ending treatment without evidence of progressive disease, unacceptable toxicity, grade 3 or more severe acute GvHD or extensive chronic GvHD.

Treatment was discontinued by 42.6% of patients most commonly because of progressive disease (19.1%) and treatment-related hypersensitivity or inflammatory reactions (20.6%).

Haematological grade 3 or 4 treatment-related adverse events (AEs) occurred in 42.6% of patients, including hemolytic anaemia in 8.8%. The most common non-haematological AEs at this severity were elevated liver enzymes (39.7%), allergy (36.9%), fever (30.9%), central neurotoxicity (14.7%), diarrhoea (10.3%) and capillary leak syndrome (10.3%).

Although 91.2% of patients reported pain in the first cycle of treatment, this fell to 38.2% by cycle 6, the researchers observe.

The team says that before the start of cycle 1 of DB, 36.8% of patients were in complete response and 52.0% maintained their response to the end of treatment, while 16.0% progressed. Of the 51.5% of patients with a partial response at the start of treatment, 40.0% achieved a complete response and 22.9% had progressive disease. Of the remaining patients with baseline nonresponsive, mixed response or progressive disease, four progressed during treatment, one achieved a complete response and one maintained stable disease but later progressed.

And among patients with evidence of disease after undergoing haplo-SCT, the objective response rate was 51.2% and the complete response rate was 34.9%, Flaadt et al write.

The researchers report that patients with a complete or partial response before immunotherapy had a better 5-year EFS rate than those without (52 and 44 vs 13%, respectively), and this was also true for OS.

By contrast, for patients who had bone marrow involvement before cycle 1, the 5-year EFS was 28% versus 52% for those with a complete response in their bone marrow.

Overall, 34 patients relapsed after a median 235 days from first DB cycle. Twenty-nine patients died from relapse, three from infection and there were individual fatalities from encephalopathy and secondary malignancy. Treatment-related mortality at day 100 and 1 year were 1.5% and 7.4%, respectively.

“DB therapy after haplo-SCT in patients with [relapsed high-risk neuroblastoma] 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”, the researchers conclude.

They add: “Further prospective and randomized trials are warranted to evaluate the contribution of each component of the approach, and larger cohorts are needed to allow better risk stratification and patient selection.”

News stories are provided by medwireNews, which is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group  

J Clin Oncol 2023; doi.10.1200/JCO.22.01630