Tandem therapy improves outcomes for children with neuroblastoma

CHICAGO — The addition of a second autologous hematopoietic stem cell transplantation to standard therapy improved survival outcomes for children with high-risk neuroblastoma, according to phase 3 trial results presented during the plenary session of the ASCO Annual Meeting.

Outcomes appeared especially improved among children who received immunotherapy following consolidation therapy.

“Neuroblastoma is a disease of early childhood, and is the most common extracranial tumor of childhood,” Julie R. Park, MD, attending physician at Seattle Children’s Hospital, professor of medicine at University of Washington School of Medicine, and director of the pediatric hematology–oncology fellowship program at University of Washington, said during a press conference. “It occurs in very young children, with a median age of less than 2 years. Clinical and biologic characteristics are used to determine prognosis and identify children who are high-risk for tumor recurrence and death from disease.”

Pediatric patients with high-risk neuroblastoma have a historical 5-year survival estimate of less than 50%. Autologous HSCT has been shown to improve EFS in this patient population, with pilot studies suggesting that tandem HSCT might further improve outcomes.

Park and colleagues conducted a multicenter randomized controlled trial to determine the benefit.

The study included data from 652 patients (median age at study entry, 3.1 years; stage IV disease, 88%; MYCN amplification, 38.2%) with newly diagnosed high-risk neuroblastoma.

All patients received induction therapy consisting of six cycles of chemotherapy, including two initial cycles of dose-intensive cyclophosphamide and topotecan, followed by peripheral blood stem cell collection.

After induction, researchers randomly assigned 355 patients to a single autologous HSCT with carboplatin, etoposide and melphalan (n = 179); or tandem autologous HSCT, with thiotepa and cyclophosphamide HSCT followed by modified carboplatin, etoposide and melphalan (n = 176).

Two hundred fifty of these patients (single, n = 129; tandem, n = 121) received dinutuximab (Unituxin, United Therapeutics) plus cytokine immunotherapy after consolidation through other Children’s Oncology Group trials.

The researchers nonrandomly assigned an additional 27 patients with non–MYCN amplified tumors (stage III, aged > 18 months; stage IV, aged 12-18 months) to single autologous HSCT with carboplatin, etoposide and melphalan.

EFS at 3 years served as the primary endpoint. OS served as a secondary endpoint.

The overall cohort had a treatment-related mortality incidence of 2.6%, including seven patients during induction and 10 patients during consolidation (single, n = 8; tandem, n = 2).

The entire cohort had a 3-year EFS from enrollment of 51% and a 3-year OS of 68.3%.

Among patients randomly assigned to treatment, more of those assigned tandem therapy achieved 3-year EFS (61.4% vs. 48.4%; P = .0082) and slightly more achieved 3-year OS (73.8% vs. 69%).

The median survival for the overall cohort was 4.6 years. OS has not been followed long enough to show a significant difference, according to Park.

Among patients who proceeded to immunotherapy, those assigned tandem therapy demonstrated significantly higher rates of 3-year EFS (73.7% vs. 56%; P = .0033) and OS (83.7% vs. 74.4%; P = .0322).

Both arms exhibited similar rates of mucosal, infectious or liver toxicities.

“Tandem transplant consolidation improves the outcomes of children with high-risk neuroblastoma,” Park said. “Toxicity or regimen-related mortality are not increased by tandem transplants, and the benefit of tandem therapy remains following anti–GD2–directed immunotherapy.” – by Cameron Kelsall

Reference:

Park JR, et al. Abstract LBA3. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.

Disclosure: The NIH provided funding for this study, which was conducted through the Children’s Oncology Group consortium. Park reports travel expenses from Roche. Please see the abstract for a list of all other researchers’ relevant financial disclosures.