Tandem Autologous Stem-Cell Transplant Boosts Event-Free Neuroblastoma Survival

By Will Boggs MD

August 29, 2019

NEW YORK (Reuters Health) - Tandem autologous stem-cell transplant (ASCT) may provide better event-free survival (EFS) in patients with high-risk neuroblastoma, compared with single ASCT, a new clinical trial shows.

"Although it was our hypothesis that tandem transplant would decrease risk for recurrence, we were surprised by the positive results, including the magnitude of the difference, and that tandem transplant improved EFS and overall survival (OS) even for those patients who received postconsolidation immunotherapy," Dr. Julie R. Park from Seattle Children's Hospital told Reuters Health by email.

Patients with high-risk neuroblastoma are typically treated with multiagent chemotherapy induction and surgical resection, consolidated high-dose chemotherapy with ASCT, posttransplant radiotherapy, and postconsolidation treatment with biological agents and immunotherapy. Despite this intensive therapy, 50% to 60% of patients relapse and more than 90% of those who relapse die of the disease.

Dr. Park and colleagues from 142 Children's Oncology Group centers in five countries investigated whether intensifying consolidation treatment with tandem transplant (two transplants six to 10 weeks apart) could improve EFS versus a single transplant in their study of 355 patients with high-risk neuroblastoma.

Among the 652 patients who had been eligible for randomization, the three-year EFS was 51.1%. The three-year EFS from the time of randomization was 54.9% for the 355 enrolled patients.

The three-year EFS from the time of randomization was significantly higher in the tandem-transplant group than in the single-transplant group (61.6% vs. 48.4%, P=0.006), the team reports in the August 27 issue of JAMA.

There were 17 deaths due to toxicity (seven during induction and 10 during consolidation therapy).

The three-year OS from the time of randomization did not differ significantly between the tandem transplant group (74.1%) and the single transplant group (69.1%).

Among patients who went on to receive isotretinoin plus anti-GD2 chimeric antibody and cytokines (immunotherapy) in two other trials, three-year ESS and OS from the time of initiating immunotherapy were significantly higher in the tandem transplant group (73.3% and 84.0%, respectively) than in the single transplant group (54.7% and 73.5%, respectively).

"Patients who meet the criteria outlined in our article (adequate organ function, no evidence of progressive disease) should be considered for tandem transplant using the regimen we report," Dr. Park said. "Intensification of therapy beyond induction therapy is required to achieve the best state of minimal residual disease to enter postconsolidation immunotherapy."

She added, "Therapy for high-risk neuroblastoma is intense and places patients at risk for late effects of therapy. While we are pleased with the continued improvement in survival for these patients, it is paramount that we continue research into novel targeted therapies (molecular or immunological) that will improve efficacy and hopefully limit late effects."

A linked editorial notes that the results "clearly demonstrate a benefit to dose intensification with tandem high-dose chemotherapy with autologous stem cell transplant within the studied patient population with high-risk neuroblastoma."

But it cautions, "The ANBL0532 trial does not address the important question as to whether tandem high-dose chemotherapy with autologous stem cell transplant results in benefit for all-comers with high-risk neuroblastoma, because just over half of the eligible patients underwent randomization."

"A separate but important challenge in interpretation of these results, as with any clinical trial results, is to understand the generalizability of findings to patient populations who may not be enrolling in trials," write Dr. Rochelle Bagatell of Children's Hospital of Philadelphia and Dr. Meredith S. Irwin from The Hospital for Sick Children in Toronto, Canada.

"The findings of this randomized clinical trial have changed current practice in North America and are expected to affect the care of children with neuroblastoma in the decades to come," they conclude.

Dr. Ami V. Desai of the University of Chicago Comprehensive Cancer Center, who recently evaluated toxicities after single versus tandem ASCT in high-risk neuroblastoma, told Reuters Health by email, "While acute toxicities were similar between those who received a single versus tandem ASCT on this study, it will be important to continue to assess both the short- and long-term toxicities associated with tandem ASCT. As alluded to by the authors, it will also be important to continue to identify the subgroups of patients with high-risk neuroblastoma who benefit the most from intensification of therapy with tandem ASCT."

"New advances in immunotherapy and targeted approaches may ultimately lead to treatments for children with high-risk neuroblastoma that prove to be effective and less toxic than tandem ASCT," she said. "However, future prospective clinical trials will be needed to determine if these alternative approaches will result in superior survival compared to tandem ASCT."

SOURCE: https://bit.ly/2UbWu7B and https://bit.ly/2NI15wK

JAMA 2019.