A phase II study evaluating whether combining an investigational anti-GD2 monoclonal antibody with induction chemotherapy improved outcomes in children with newly diagnosed high-risk neuroblastoma found that the therapy significantly improved 2-year event-free survival. Furman et al published the findings in Clinical Cancer Research.

Neuroblastoma is the most common solid tumor found in pediatric patients, and it affects more than 700 children in the United States each year. The current standard treatment for high-risk neuroblastoma—which is defined by the presence of tumor MYCN amplification or children aged older than 18 months with metastatic disease at diagnosis—includes high-dose induction chemotherapy, surgery, and consolidation with myeloablative chemotherapy, autologous hematopoietic cell transplant, radiotherapy, and treatment of minimal residual disease with a monoclonal antibody that targets disialoganglioside GD2 on neuroblasts. Despite improvement in 2-year event-free survival with this therapy (66% vs 46%; P = .01) nearly 50% of patients experience relapse and die from the disease.

Methods

The researchers conducted a prospective, nonrandomized, single-arm, two-stage, phase II clinical trial. They enrolled 43 patients aged 19 years old or younger with newly diagnosed high-risk neuroblastoma. The patients received six courses of induction chemotherapy in combination with a humanized antidisialoganglioside monoclonal antibody—hu14.18K322A—followed by granulocyte macrophage colony-stimulating factor (GM-CSF) and low-dose interleukin-2 (IL-2). Consolidation was performed with a busulfan/melphalan preparation. An additional course of hu14.18K322A was administered with patient-derived natural killer cells during consolidation. The patients were then administered hu14.18K322A, GM-CSF, IL-2, and isotretinoin.

Results

Forty-two patients received hu14.18K322A and induction chemotherapy. The regimen was well tolerated, with continuous-infusion narcotics adjusted to patient tolerance. Thirty-two patients achieved partial response or better after the first two chemoimmunotherapy courses (76.2%; 95% confidence interval [CI] = 60.6­–88.0). This was accompanied by primary tumor volume reductions (median = −76%; range, −100%­ to 5%).

Of 35 patients with stage IV disease who completed induction; 31 had end-of-induction Curie scores of 2 or less. No patients experienced progression during induction. Two-year event-free survival was 85.7% (95% CI = 70.9–93.3).

“Adding hu14.18K322A to induction chemotherapy produced early partial response or better in most patients, reduced tumor volumes, improved Curie scores at the end of induction, and yielded an encouraging 2-year event-free survival. These results, if validated in a larger study, may change the standard of care for children with high-risk neuroblastoma,” concluded the study authors.

Translational Relevance

“The results were beyond our wildest dreams,” said Wayne L. Furman, MD, member of the Department of Oncology at St. Jude Children’s Research Hospital and lead author of this study, in a statement. “Many of these kids at diagnosis had multiple metastases all over their body visualized on metaiodobenzylguanidine scans, and after only two courses, many of these were completely clear. I think adding the anti-GD2 antibody starting with the first cycle of treatment is the way to treat these patients, certainly in our experience.”

Dr. Furman is the corresponding author of the Clinical Cancer Research article.

Disclosure: Funding for this study was provided by St. Jude Children’s Research Hospital Comprehensive Cancer Center Support Grant, American Lebanese Syrian Associated Charities, Cookies for Kids’ Cancer, and Cure Childhood Cancer Foundation. For full disclosures of the study authors, visit clincancerres.aacrjournals.org.