Feasibility and Tolerability of Chemoimmunotherapy Given During Induction for Treatment of Patients With High-Risk Neuroblastoma: A Report From the Children's Oncology Group
Sara M. Federico, Arlene Naranjo, Fan F. Zhang, Paul Sondel, Ankita Shahi, Megan Lilley, Steve Braunstein, Christopher Tinkle, Gregory Yanik, Hiroyuki Shimada, Meredith S. Irwin, Alice L. Yu, Araz Marachelian, Shahab Asgharzadeh, Ami V. Desai, Jason Jarzembowski, Daphne Haas-Kogan, Tamarah J. Westmoreland, Marguerite T. Parisi, Barry Shulkin, Michael Acord, Wayne Furman, Steven G. DuBois, Rochelle Bagatell, Julie R. Park, Suzanne ShustermanPurpose
The addition of the anti-GD2 antibody dinutuximab (DIN) to postconsolidation therapy led to improved event-free survival (EFS) for patients with high-risk neuroblastoma (HRNBL). The combination of DIN with chemotherapy (chemoimmunotherapy) results in objective responses in patients with recurrent/refractory neuroblastoma. We evaluated the feasibility of administering chemoimmunotherapy during induction for HRNBL in a multicenter trial.
Methods
Children's Oncology Group (COG) ANBL17P1 was a prospective, single-arm, limited institution pilot study to assess tolerability and feasibility of administering DIN and sargramostim with induction chemotherapy cycles 3-5. The primary end point of tolerability was assessed as the occurrence of a predefined unacceptable toxicity or toxic death during DIN-containing cycles. Feasibility was assessed as ability to receive ≥75% of planned DIN doses. Revised International Neuroblastoma Response Criteria were used to assess response.
Results
Forty eligible, evaluable patients with newly diagnosed HRNBL were enrolled at eight sites from January 2019 to June 2020. The most common DIN-related grade ≥3 toxicities during induction cycles 3-5 included fever (30.0%) and pain (7.5%). There were no unacceptable toxicities or toxic deaths during induction cycles 3-5. Patients received 92.0%-101.8% of intended induction DIN doses. This regimen was therefore deemed both feasible and tolerable. Thirty-seven patients completed all end-of-induction evaluations; 13 had complete response (CR), 22 partial response (PR), one minor response (MR), zero stable disease, and one progressive disease. The overall end of induction CR + PR rate was 87.5%. The 3-year EFS was 52.5% ± 7.9%.
Conclusion
Administration of DIN with COG induction cycles 3-5 for patients with newly diagnosed HRNBL was tolerable and feasible. This approach is currently being evaluated in a COG randomized phase III trial.