Adding hu14.18K322A to induction chemotherapy may improve outcomes in pediatric patients with high-risk neuroblastoma, according to research published in the Journal of Clinical Oncology.
A majority of patients had a partial response or better after receiving chemotherapy plus hu14.18K322A, a humanized anti-disialoganglioside monoclonal antibody.
Researchers also reported an “encouraging” 3-year event-free survival rate for these patients, who went on to transplant and radiotherapy after induction.
“These results, if validated in a larger study, may be practice-changing,” the researchers wrote.
The phase 2 study (ClinicalTrials.gov Identifier: NCT01857934) included 64 patients with newly diagnosed, high-risk neuroblastoma. They had a median age of 3.1 years (range, 0.5-15.2 years). Most patients were boys (58%), White (67%), and had stage IV disease (87%).
Patients received induction with cyclophosphamide, topotecan, cisplatin, etoposide, doxorubicin, and vincristine. They also received 4 daily doses of hu14.18K322A with each cycle of chemotherapy and continuous infusions of opioids approximately 30 minutes before the antibody infusions.
After each cycle, patients received daily granulocyte-macrophage colony-stimulating factor and interleukin-2 once every other day for 6 doses. They underwent stem cell collection after induction cycle 2 or 4, and primary tumors were resected at any time point after cycle 2.
Patients then received busulfan and melphalan conditioning, followed by autologous stem cell transplant (ASCT). Some patients received an additional cycle of daily hu14.18K322A (days 2-5) after ASCT and natural killer cell infusions (donated by parents) when available (on day 4 after ASCT).
After ASCT recovery (typically within 43 days), patients received intensity-modulated radiation therapy or scanned proton beam radiation therapy (2340 cGy in 180 cGy fractions). Patients with macroscopic residual disease after induction received an additional 720 cGy to those sites.
Safety and Efficacy Outcomes
Toxicities attributed to hu14.18K322A infusion included pain (10%), hypoxia (6%), infusion-related reactions (4%), hypotension (3%), and cough (1%).
There were 63 patients evaluable for response after 2 cycles of induction, and 66.7% of them (n=42) had a partial response or better. All but 1 patient had a decrease in primary tumor volume at cycle 2.
At the end of induction, 96.8% of patients (60/62) had a partial response or better, including 65% (n=40) with metastatic complete responses.
There were 13 patients who had progressive disease during or after treatment, and 4 patients died of progression.
Two patients died of complications from therapy — 1 due to transplant-related complications and 1 from non-neutropenic sepsis.
The 3-year event-free survival rate was 73.7%, and the 3-year overall survival rate was 86%.
“These results, if validated in a larger study, may change the standard of care for children with HR [high-risk] neuroblastoma,” the researchers concluded.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Furman WL, McCarville B, Shulkin BL, et al. Improved outcome in children with newly diagnosed high-risk neuroblastoma treated with chemoimmunotherapy: Updated results of a phase II study using hu14.18K322A. Published online December 6, 2021. J Clin Oncol. doi:10.1200/JCO.21.01375