Julie R. Park, MD

In children with high-risk neuroblastoma, tandem autologous stem cell transplant (ASCT) improved event-free survival rates in the ANBL0532 trial from the Children’s Oncology Group. The study was presented at the plenary session of the 2016 ASCO Annual Meeting by Julie R. Park, MD, of Seattle Children’s Hospital and the University of Washington School of Medicine.¹

“Tandem transplant consolidation improves outcomes in patients with high-risk neuroblastoma who survive induction without disease progression or severe induction-related toxicity. Toxicity or regimen-related mortality is not increased by tandem transplant, and the benefit of tandem ASCT remains, following anti-GD2–directed immunotherapy,” Dr. Park declared.

Neuroblastoma is responsible for greater than 10% of pediatric cancer–related mortality, and fewer than 50% of patients will survive, even with aggressive therapy, she noted.

Previous studies have shown that treatment intensification in the way of a single ASCT improved event-free survival. “We hypothesized that further intensification with tandem ASCT could improve outcomes even more,” Dr. Park said.

Study Details

The study enrolled 652 patients with newly diagnosed high-risk neuroblastoma. Median age was 37 months; 36% of patients had MYCN gene amplification; and 88% had stage IV disease.

Patients underwent six cycles of chemotherapy, beginning with two cycles of cyclophosphamide and topotecan. Peripheral blood stem cells were harvested at that time, after which induction was continued with alternating cycles of cisplatin/etoposide and cyclophosphamide/vincristine/doxorubicin, followed by surgery.

Patients were then randomized to undergo a single ASCT with carboplatin/etoposide/melphalan (CEM) or tandem ASCT with cyclophosphamide/thiotepa followed by a modified regimen of carboplatin/etoposide/melphalan (Cy-THIO/mCEM). The modified arm had lower doses of carboplatin (1,500 mg/m²), etoposide (1,200 mg/m²), and melphalan (180 mg/m²).

All patients received radiotherapy at the primary tumor site. The 27 patients with non–MYCN-amplified stage 3 or 4 tumors were nonrandomly assigned to receive the single ASCT regimen.

Approximately 70% of patients who completed induction and consolidation entered a second trial evaluating post-consolidation immunotherapy with isotretinoin alone compared with isotretinoin pus dinutuximab (Unituxin) and cytokines, ie, GD2-directed immunotherapy. This group was evaluated to determine whether tandem transplant provides additional benefit to immunotherapy.

Primary Endpoint Met

Three-year event-free survival was 61.4% with tandem ASCT and 48.4% with single ASCT (P = .0081). Overall survival at 3 years was 74.0% and 69.1%, respectively (P = .1850), which was not a significant ­improvement.

Tandem transplant consolidation improves outcomes in patients with high-risk neuroblastoma who survive induction without disease progression or severe induction-related toxicity.

— Julie R. Park, MD

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The benefit of tandem ASCT was preserved in patients who also received GD2-directed immunotherapy. In these patients, 3-year event-free survival was 73.7% with tandem ASCT and 56.0% with single ASCT (P = .0033); 3-year overall survival was 83.7% and 74.4%, respectively (P = .0322).

Tandem transplant was tolerated well, with no additional nonhematologic toxicities compared with single transplant. There were seven deaths (4.1%) in the cohort receiving a single ASCT and two (1.2%) among those undergoing tandem transplant (P = .17). ■

Disclosure: Dr. Park has received travel expenses from Roche.

Reference

1. Park JR, Kreissman SG, London WB, et al: A phase 3 randomized clinical trial of tandem myeloablative autologous stem cell transplant using peripheral blood stem cell as consolidation therapy for high-risk neuroblastoma: A Children’s Oncology Group study. 2016 ASCO Annual Meeting. Abstract LBA3. Presented June 5, 2016.