Responses to Irinotecan, Temozolomide, Dinutuximab, and GM-CSF Regimen in Patients With Relapsed High-Risk Neuroblastoma

Get Permission

In a U.S. retrospective study reported in the Journal of Clinical Oncology, Lerman et al found that half of patients with relapsed high-risk neuroblastoma had an objective response to a regimen comprising irinotecan, temozolomide, dinutuximab, and granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF).

As stated by the investigators, “Although chemoimmunotherapy is widely used for treatment of children with relapsed high-risk neuroblastoma, little is known about timing, duration, and evolution of response after I/T/DIN/GM-CSF therapy.”

Study Details

The study included 146 patients (median age at diagnosis = 51 months, interquartile range = 31–72 months) who received at least one cycle of I/T/DIN/GM-CSF for relapsed disease outside the context of a clinical trial at 13 U.S. sites between January 2015 and June 2020. Patients with primary refractory disease who progressed through induction were excluded. Responses were evaluated using the International Neuroblastoma Response Criteria.

Key Findings

Patients received a median of 4.5 cycles of treatment (range = 1–31 cycles).

Objective response was achieved in 71 patients (49%), including complete response in 29%, partial response in 14%, and minor response in 5%. An additional 21% of patients had stable disease. Median duration of response was 15.9 months (95% confidence interval [CI] = 14 months to not evaluable).  

Among patients with stable disease or better at first response evaluation, 22% had improved response at subsequent evaluation, including:

  • Five patients (13%) with initial stable disease (improvement to complete response in three, partial response in one, and minor response in one)
  • Three patients (33%) with initial minor response (improvement to complete response in each)
  • Improvement to complete response in 14 patients (41%) with initial partial response.

Among all patients, median progression-free survival was 13.1 months (95% CI = 9.8–16.5 months), with 6-month, 1-year, and 2-year rates of 62%, 50%, and 28%, respectively. Among patients with objective response, median progression-free survival was 15.9 months (95% CI = 14 months to not evaluable), with 6-month, 1-year, and 2-year rates of 86%, 68%, and 44%, respectively.

Among 21 patients with objective response (14 with complete and 7 with partial response) who discontinued treatment and received no further anticancer therapy, median progression-free survival after discontinuation of I/T/DIN/GM-CSF was 10.4 months (95% CI = 7.4 months to not evaluable).  

The investigators concluded, “Approximately half of patients receiving I/T/DIN/GM-CSF for relapsed high-risk neuroblastoma had objective responses. Patients with initial stable disease were unlikely to have an objective response, but less than one of three patients with minor response/partial response on first evaluation ultimately had complete response. I/T/DIN/GM-CSF was associated with extended progression-free survival in responders both during and after discontinuation of treatment. This study establishes a new comparator for response and survival in patients with relapsed high-risk neuroblastoma.”  

Benjamin J. Lerman, MD, MS, of the Children’s Hospital of Philadelphia and University of Pennsylvania, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: For full disclosures of the study authors, visit


The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.