Advertisement

Outcomes With Postconsolidation Dinutuximab-Based Immunotherapy for Neuroblastoma


Advertisement
Get Permission

In an analysis reported in the Journal of Clinical Oncology, Desai et al described outcomes with postconsolidation dinutuximab-based immunotherapy for high-risk neuroblastoma in a cohort of patients from the Children’s Oncology Group ANBL0032 trial following cessation of randomized treatment.

Study Details

In the randomized trial, the addition of immunotherapy with the anti-GD2 chimeric antibody dinutuximab, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-2 (IL-2) to isotretinoin (n = 113) significantly improved 2-year event-free survival (66% vs 46%, P = .01) and overall survival (86% vs 75%, P = .02) vs standard treatment with isotretinoin (n = 113). Random assignment was halted, and the immunotherapy arm remained open.

In the current analysis, 1,183 patients with a pre–autologous stem cell transplantation (ASCT) response (excluding bone marrow) of partial response or better received immunotherapy between 2009 and 2015. Treatment consisted of six cycles, with dinutuximab given in cycles 1 through 5, GM-CSF in cycles 1, 3, and 5, IL-2 in cycles 2 and 4, and isotretinoin in all cycles.

Key Findings

Among all patients, 5-year event-free survival was 61.1% ± 1.9% and 5-year overall survival was 71.9 ± 1.7%. Among 662 patients aged ≥ 18 months at diagnosis with International Neuroblastoma Staging System stage 4 disease, 5-year event-free survival and overall survival were 57.0% ± 2.4% and 70.9% ± 2.2%, respectively.

Event-free survival at 5 years was better among 770 patients with a complete response (n = 352) or very good partial response (n = 418) pre-ASCT vs 413 with a partial response (64.2% ± 2.2% vs 55.4% ± 3.2%, P = .0133). No difference in 5-year overall survival was observed between these two groups (72.7% ± 2.1% vs 70.5% ± 2.9%, P = .3811).

Among patients with available data, event-free survival was improved among patients with higher peak dinutuximab levels during cycle 1 (P = .034) and those with a high affinity FCGR3A genotype (P = .0418), with overall survival benefits not achieving significance (P = .0721 and P = .0806, respectively). Human anti–chimeric antibody status did not correlate with event-free (P = .6327) or overall survival (P = .8531).

Grade ≥ 3 fever (33.6% vs 15.5%), allergic/hypersensitivity reactions (21.0% vs 12.4%), hypotension (13.7% vs 9.2%), and capillary leak syndrome (11.0% vs 5.2%) were significantly more common (all P < .0001) during cycles with IL-2 vs those with GM-CSF). No treatment-related deaths were observed.

The investigators concluded: “Analysis of a cohort assigned to immunotherapy after cessation of random assignment on ANBL0032 confirmed previously described survival and toxicity outcomes. [Event-free survival] was highest among patients with end-induction complete response/very good partial response. Among patients with available data, higher dinutuximab levels and FCGR3A genotype were associated with superior [event-free survival]. These may be predictive biomarkers for dinutuximab therapy.”

Alice L. Yu, MD, PhD, Department of Pediatrics, University of California, San Diego, is the corresponding author for the Journal of Clinical Oncology article. 

Disclosure: The study was supported by grants from the National Cancer Institute and St Baldrick’s Foundation. For full disclosures of the study authors, visit ascopubs.com.

 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
Advertisement

Advertisement



Advertisement