MSK Kids has one of the largest teams of neuroblastoma experts and treats the highest volume of pediatric patients with neuroblastoma in the United States. Today, more than half of children with metastatic neuroblastoma survive, a 10-fold improvement since the 1980s, primarily due to translational and clinical research advances at MSK Kids.
Research continues apace as investigators seek new ways to improve outcomes and the quality of life for pediatric patients with high-risk neuroblastoma. Highlights of the latest clinical and molecular research advances are as follows:
- Three phase 2, MSK Kids-exclusive clinical trials of novel treatment approaches.
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New studies demonstrating that:
Avoiding myeloablative therapy after Rapid COJEC intensive induction does not adversely affect survival.
Naxitamab plus granulocyte-macrophage colony-stimulating factor (GM-CSF) shows significant efficacy with a manageable safety profile.
A newly-discovered ultra-high-risk subset of patients may inform stratification for trials of novel TERT-targeted treatments.
MSK Kids-Exclusive Neuroblastoma Clinical Trials in Progress
MSK Kids is currently recruiting participants for three phase 2 clinical trials for pediatric and young adult patients with neuroblastoma. These trials are not available at other centers:
- A clinical trial of the immunological adjuvant OPT-821 (QS-21) and a bivalent ganglioside vaccine in combination with the oral dietary supplement beta-glucan for pediatric patients with high-risk neuroblastoma in remission. The goal of the study (NCT06057948) is to determine the optimal oral beta-glucan schedule for maximizing anti-GD2 antibody titers among patients in first or second remission. MSK Kids pediatric hematologist-oncologist Brian Kushner, MD, is the principal investigator of the study, which seeks to enroll 94 patients. Learn more. Results from a previous phase 2 study, published in JAMA Oncology, showed that adding oral beta-glucan during vaccine priming increased the anti-GD2 IgG1 titer among genetic responders without any added toxic effects. (1)
- A clinical trial of N10, a novel, reduced-therapy regimen for treating patients with high-risk neuroblastoma. Patients receive three different chemotherapy combinations across four cycles. After cycle 3, stem cells are collected, and patients undergo surgery to remove the tumor. After cycle 4, patients receive two cycles of naxitamab and GM-CSF, followed by response-based radiation or other treatment. Led by principal investigator Dr. Kushner, the study (NCT06528496) seeks to enroll 45 patients. Learn more.
- An open access study assessing the targeted radiotherapy 131I- metaoidobenzylguanidine (I-MIBG) in patients with neuroblastoma, malignant pheochromocytoma, or malignant paraganglioma that has recurred or is resistant to standard treatments. Led by pediatric hematologist-oncologist Ellen Basu, MD, PhD the study (NCT00107289) began in 2004 and seeks to enroll 200 patients. Learn more.
Avoiding MAT After Rapid COJEC Does Not Compromise Survival in High-Risk Neuroblastoma
Previously, Dr. Kushner, pediatric hematologist-oncologist Shakeel Modak, MD, Chief of the Neuroblastoma Service, and colleagues at MSK Kids reported that avoiding transplant after standard induction does not impact long-term overall survival (OS) for patients with high-risk neuroblastoma. (2)
Recently, they published the first report on Rapid COJEC (cisplatin, vincristine, carboplatin, etoposide, and cyclophosphamide) intensive induction chemotherapy without myeloablative therapy (MAT) for pediatric patients with high-risk neuroblastoma. Rapid COJEC is the standard induction regimen used in Europe.
The analysis showed that avoiding MAT after Rapid COJEC does not adversely affect event-free survival (EFS) or OS. Results of the retrospective study were published in July 2025 in the International Journal of Cancer. (3)
The investigators evaluated outcomes for 28 patients with no prior history of progressive disease. After Rapid COJEC, 10 patients achieved a complete remission of distant disease (Group 1) and 18 had persistence of metastatic disease (Group 2). (3) Notably, all ten patients in Group 1 remained event-free and in first complete remission at a median of 3.7 years post-diagnosis (range, 1.7 to more than 8 years). (3)
Results for the 18 patients in Group 2 showed that overcoming persistent metastatic disease post-COJEC presents a greater challenge. Twelve of the 18 patients in Group 2 remained relapse-free at a median of 2.4 years (range 1.4 to more than 5.8 years) post-diagnosis, including three who developed secondary cancers (two patients developed myelodysplastic syndrome, which was successfully treated, and one patient had thyroid cancer). Six patients developed progressive disease at a median of 1.3 years post-diagnosis, of which four are in second complete remission after salvage treatment with chemotherapy, radiotherapy, and anti-GD2 immunotherapy, and two died of progressive disease. The three-year EFS and OS rates in Group 2 were 62% and 94%, respectively. (3)
“Group 1 may have experienced better outcomes since four of the 10 patients had MYCN-amplified localized neuroblastoma, which we previously reported is associated with an excellent prognosis with anti-GD2 mAb without MAT,” said Dr. Kushner.
MAT is included in the treatment programs of the Children’s Oncology Group (COG) and the Societe Internationale d’Oncologie Pediatrique Europe Neuroblastoma (SIOPEN) for patients with high-risk neuroblastoma. By contrast, MSK Kids discontinued MAT in 2003, based on positive results with anti-GD2 mAb plus GM-CSF, which demonstrated improved outcomes in sequential clinical trials, whereas treatment plans including MAT did not. (4)
“At MSK Kids, we continue to look for new ways to reduce chemotherapy and avoid long-term adverse sequelae, without compromising survival outcomes,” said Dr. Kushner. “This goal is realistic given recent advances with anti-GD2 mAbs plus GM-CSF, which are highly effective against neuroblastoma that persists in bone metastases, as well as the GD2/GD3 ganglioside vaccine pioneered at MSK and new therapies that show promise without adding toxicity, including difluoromethylornithine, and ALK inhibitors.”
Naxitamab plus GM-CSF Shows High Efficacy in International Trial
Preliminary efficacy results from two phase 2 clinical trials (Trial 12-230, NCT01757626 and Trial 201, NCT03363373) supported the FDA approval of naxitamab plus GM-CSF for pediatric and adult patients with high-risk neuroblastoma with metastatic disease in the bone or bone marrow. (5) Most recently, the prespecified analysis of Trial 201 found that naxitamab plus GM-CSF demonstrated statistically significant efficacy with a manageable safety profile. Among the 52 participants, 58% had refractory disease and 42% had relapsed disease. The overall response rate was 50%, with complete and partial responses observed in 38% and 12% of participants, respectively. The one-year OS and progression-free survival (PFS) rates were 93% and 35%, respectively. (6)
Safety outcomes were in line with previous reports. The most commonly reported grades 3 to 4 adverse events with potential to cause severe clinical complications were hypotension and bronchospasm, although most (70%) of the hypotension events were resolved within one hour. Grade 3 pain was reported frequently, a known effect of anti-GD2 mAb therapy due to GD2 expression on peripheral nerve fibers. While intense, pain during infusions dissipated within 15 minutes of treatment completion and did not lead to any discontinuation. The authors noted that naxitamab administration requires a coordinated, multidisciplinary team for close monitoring and immediate intervention. (5)
“The clinically meaningful response rates in patients with metastatic disease in the bone or bone marrow were very encouraging,” said Dr. Kushner, the senior author of the paper published in Nature Communications in February 2025. “Keep in mind that the goal of Trial 201 was to evaluate the impact of naxitamab plus GM-CSF without concurrent chemotherapy in patients without soft tissue disease at enrollment or active progressive disease that requires intensive, multimodal treatment plans.”
MSK physician-scientist Nai-Kong Cheung invented the monoclonal antibody 3F8 and developed the humanized version (hu3F8 or naxitamab), which earned breakthrough therapy designation from the U.S. Food and Drug Administration in 2018 and accelerated approval in 2020. MSK licensed naxitamab to Y-mAbs Therapeutics in 2015 with the goal to increase its availability world-wide.
Since then, the drug has been approved in many other countries, including Israel, China, Brazil, and Mexico, in combination with GM-CSF, for treating pediatric and adult patients with relapsed or refractory high-risk neuroblastoma in the bone who have shown a partial or minor response or stable disease before therapy. Read more about the naxitamab invention at MSK.
Identifying TERT Promoter Mutations May Improve Treatment Stratification
Telomere maintenance mechanisms, including MYCN amplification via upregulated telomerase reverse transcriptase (TERT) expression, confer immortality in neuroblastoma cells. MSK Kids researchers were the first to identify TERT promoter mutations (TERT-PM) in a study of the clonal evolution of high-risk neuroblastoma during metastatic spread. (7)
For their present study, published in July 2025 in JCO Precision Oncology, (8) principal investigator Dr. Modak and colleagues evaluated TERT expression and clinical outcomes. They evaluated the presence of TERT-PM and TERT rearrangements (TERT-RA) in more than 600 neuroblastoma tumors from individual pediatric patients using the targeted exome sequencing assay MSK IMPACT® and whole genome sequencing. Overall, they found TERT-PM in 17 of 603 tumors (2.8%) and TERT-RA in 31 of 168 tumors (18.4%). TERT-PM co-occurred with MYCN amplification (MYCN-A) in 53% of cases, whereas only 1 in 31 TERT-RA cases also had MYCN-A. (7)
Next, the investigators studied the associated clinical outcomes to see whether characterizing patients with neuroblastoma harboring somatic TERT-PM may improve stratification. They found that despite treatment with risk-appropriate therapy, median PFS was similarly poor at nine months for patients with TERT-PM or TERT-RA. However, OS was significantly worse for those with TERT-PM. (7)
“Our study revealed that patients harboring neuroblastoma tumors with TERT-PM constitute an ultra-high risk group, suggesting that routine testing for these mutations may refine risk stratification and help identify patients who may benefit from escalation of therapy,” Dr. Modak said.
Access disclosures for Dr. Kushner and Dr. Modak.