Addition of chemo-immunotherapy to standard induction chemotherapy for high-risk neuroblastoma.
Authors: Fernandez Karen S. , Sabnis Amit J. , Titapiwatanakun Ruetima , Baker Katherine , Tcheng Wendy 
Published: June 2022

e22009

Background: The outcome of high risk neuroblastoma (HR-NBL) remains poor despite the use of multimodality approach. Improved end-induction response (EOI-R) after standard induction chemotherapy (SIC) is associated with longer survival1. Post-induction curie score (CS) > 2 is associated with inferior outcome2. The combination of chemo immunotherapy (CIT) with irinotecan/temodar/dinutuximab/GMCSF (ITDG) demonstrated an objective response of 53% in patients with relapsed/refractory disease3, however, the specific impact of the addition of CIT in improving EOI-R permitting continuation of therapy with surgery, ASCT, radiotherapy, and consolidative immunotherapy has not been systematically evaluated. Here we present the outcome of 8 patients who received SIC followed by CIT that achieved a CS < 2 prior to ASCT and were able to complete multimodality therapy. Methods: Single-site retrospective review of HR-NBL patients that failed to achieve adequate EOI-R after SIC during 2016 – 2021. Results: 21 patients with HR-NBL treated with SIC were identified. 8/21 patients (38%) failed to achieve adequate EOI-R: 3 patients were deemed to have partial response (PR), and unresectable tumors after 5 cycles SIC, 3 patients achieved complete remission (CR) of primary tumor but had CS > 2 at the EOI, 1 patient had stable disease (SD) with CS > 2 after 4 cycles of SIC, and 1 patient progressive disease (PD), and CS > 2 after 3 cycles of SIC. All patients received CIT with ITDG (2 – 6 cycles). The 3 patients with unresectable tumors, and 2 patients with CS > 2 achieved adequate response with CS < 2 after 2-4 CIT cycles. They were able to undergo resection and achieve CR. The patient with PD achieved CR of primary tumor after 2 ITDG-cycles allowing surgical resection, and ultimately achieved a CS = 0 after 4 additional ITDG-cycles. The patient with SD received 6 ITDG-cycles but remain SD with CS = 24 and went on to receive MIBG therapy. 5/8 patients were able to proceed with ASCT, radiation and, post consolidative immunotherapy. One patient did not receive ASCT due to surgery-related acute kidney injury but completed radiation and consolidative immunotherapy. Post CIT progression free survival (PFS) ranges from 4 – 56 months. Three patients are free of disease at 17, 38 and 36 months after completing post consolidation immunotherapy, 3 patients completed post consolidation immunotherapy and 1 has received 2 cycles. Conclusions: This short retrospective observational analysis demonstrate that the addition of CIT with ITDG in children with HR-NBL with less than PR, SD and/or PD after SIC is feasible, aids in achieving end-induction goals of CR and CS < 2, and permits many patients to complete consolidative ASCT, radiation, and post-consolidation immunotherapy. While the COG is planning to evaluate addition of ITDG in induction therapy, patients currently being treated off study may benefit from the addition of ITDG after SIC to improve EOI-R.