In a single-institution phase II trial reported in the Journal of Clinical Oncology, Furman et al found that the addition of the humanized antidisialoganglioside monoclonal antibody hu14.18K322A to chemotherapy produced high rates of early and end-of-induction response and event-free survival in children with newly diagnosed high-risk neuroblastoma.
Study Details
The trial included 64 patients at St. Jude Children’s Research Hospital enrolled beginning in May 2013, with the last patient completing therapy in July 2019. Patients received six cycles of induction chemotherapy coadministered with infused hu14.18K322A, granulocyte-macrophage colony-stimulating factor (GM-CSF), and low-dose interleukin-2 (IL-2).
Consolidation included busulfan and melphalan; a total of 31 patients received an additional cycle of parent-derived natural killer cells with hu14.18K322A during consolidation. Postconsolidation treatment included hu14.18K322A, GM-CSF, IL-2, and isotretinoin.
All patients received a continuous infusion of opioids approximately 30 minutes before antibody infusions. Radiation therapy was administered at the end of consolidation.
Adding hu14.18K322A to induction chemotherapy improved early objective responses, significantly reduced tumor volumes in most patients, improved end-of-induction response rates, and yielded an encouraging 3-year event-free survival. These results, if validated in a larger study, may be practice-changing.— Furman et al
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Key Findings
Partial response or better after the first two chemoimmunotherapy cycles (early response) was observed in 42 (66.7%, 95% confidence interval [CI] = 55.0%–78.3%) of 63 evaluable patients. The early response rate was significantly higher than that observed after two chemotherapy induction cycles in a previous Children’s Oncology Group (COG) study (ANBL0532) in this setting (39.1%; P < .0001).
Primary tumor volume was reduced by a median of 75%. Median peak hu14.18K322A serum levels in cycle 1 were correlated with early response (P = .0154).
At the end of induction therapy, partial response or better was observed in 60 (96.8%, 95% CI = 88.8%–99.6%) of 62 evaluable patients; no patients exhibited disease progression during induction. At 3 years, event-free survival was 73.7% (95% CI = 60.0%–83.4%) and overall survival was 86.0% (95% CI = 73.8%–92.8%).
The end of induction response rate and 3-year event-free survival rate compared favorably with rates of 80% and 55.6%, respectively, observed in a recent study in 146 patients evaluating busulfan/melphalan and autologous hematopoietic stem cell transplantation after a five-cycle COG induction regimen.
Toxicities attributed to antibody infusion in the total of 379 cycles included pain (10%; 38 episodes), hypoxia (6%; 21 episodes), infusion-related reactions (4%; 14 episodes), hypotension (3%; 12 episodes), and cough (1%; 4 episodes).
The investigators concluded, “Adding hu14.18K322A to induction chemotherapy improved early objective responses, significantly reduced tumor volumes in most patients, improved end-of-induction response rates, and yielded an encouraging 3-year event-free survival. These results, if validated in a larger study, may be practice-changing.”
Wayne L. Furman, MD, of the Department of Oncology, St. Jude Children’s Research Hospital, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute, American Lebanese Syrian Associated Charities, and Cookies for Kids’ Cancer and Cure Childhood Cancer Foundation. For full disclosures of the study authors, visit ascopubs.org.
