Double Stem Cell Transplant Improves Outcomes in High Risk Neuroblastoma

Children with high risk neuroblastoma achieved improved outcomes after receiving a second autologous stem cell transplant (ASCT) in addition to standard therapy.

A study presented at the American Society of Clinical Oncology (ASCO) Annual Meeting reported 61.4% of patients evaluated were alive and cancer free at 3 years after receiving a double transplant.

The phase 3 trial was conducted by the Children’s Oncology Group and funded by the National Cancer Institute (NCI). The study enrolled children with high risk neuroblastoma who had a median age of 3.1 years. A majority of patients (88%) had stage 4 cancer and 38.2% had MYCN amplification.

Patients were administered 6 cycles of a multi-agent induction chemotherapy regimen, plus an initial 2 cycles of high dose cyclophosphamide/topotecan, followed by the harvesting of stem cells. Next, patients were randomized to receive either a single ASCT with carboplatin-etoposide-melphalan (CEM) chemotherapy or a double (tandem) ASCT with thiotepa-cyclophosphamide before the first ASCT followed by a modified CEM chemotherapy prior to the second ASCT.

In the tandem ASCT arm, patients were given 2 transplants in the span of 6 to 8 weeks. There were 129 of 179 patients in the single ASCT arm who were subsequently enrolled in a trial delivering anti-GD2 (dinutuximab) plus cytokine immunotherapy after single transplant consolidation therapy.

Following tandem transplant consolidation therapy, 121 out of 176 patients received the same immunotherapy. The primary endpoint was 3-year event free survival (EFS).

The study defined event as worsening or recurrence of cancer, the diagnosis of a second cancer, or death from any cause. The results of the study found that the 3-year EFS from enrollment was 51%, while the 3-year overall survival (OS) was 68.3% in all study patients.

In the tandem group, the 3-year EFS rate from the time of randomization was 61.4%, significantly higher than the single transplant group (48.4%).

The 3-year OS rate was slightly higher in the tandem group than the single transplant group at 74% versus 69.1%, respectively. However, the differences were not statistically significant.

“We know that most neuroblastoma recurrences occur within 2 to 3 years from diagnosis and that patients who had not had a recurrence at 3 years have a better chance of long term survival,” said lead study author Julie R. Park, MD. “The study was not designed to observe a difference in overall survival, as this would take many years and cannot be adequately controlled for additional therapies received after an initial disease recurrence.”

Researchers note that they will continue to follow the study patients for 10 years. The outcomes of the trial were found to be generally better in patients who enrolled in the immunotherapy trial, with anti-GD2 antibody plus cytokines after the transplant.

These patients showed a 3-year EFS rate significantly higher in a tandem transplant (73.2%) compared with a single transplant (55.5%). The 3-year OS was significantly higher in the tandem transplant group (85.6%) than the single transplant group (75.8%).

Severe toxicities were similar between groups. Patients who received a tandem transplant showed fewer treatment-related deaths (2) than the single transplant group (8).

“This finding will change the way we treat children with high risk neuroblastoma in North America, which still claims many young lives and is in urgent need for better treatments,” Park said. “However, the regiment we use for high risk neuroblastoma is also the most aggressive and toxic regimen we give to children with cancer. For that reason, future research needs to focus on both exploring possible late effects of the current therapy and developing newer less toxic therapies.”