2329 - A Phase III Study of 131I-Metaiodobenzylguanidine (131I-MIBG) or Lorlatinib Added to Intensive Therapy for Children with Newly Diagnosed High-Risk Neuroblastoma (ANBL1531)
Presenter(s)
S. E. Braunstein1, J. T. Lucas Jr2, J. E. Panoff3, A. Naranjo4, K. Karolczuk5, E. Greengard6, Y. Mosse7, W. Fitzgerald8, K. K. Matthay9, M. Granger10, M. E. Hogarty8, M. Irwin11, F. Zhang12, B. Weiss13, J. R. Park10, G. Yanik14, R. Bagatell15, S. G. Dubois16, and C. E. Hill-Kayser17; 1Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 2Department of Radiation Oncology, St. Jude Children’s Research Hospital, Memphis, TN, 3Department of Radiation Oncology, Miami Cancer Institute, Miami, FL, 4Children's Oncology Group Statistics and Data Center, University of Florida, Gainesville, FL, 5Imaging and Radiation Oncology Core (IROC), Lincoln, RI, 6University of Minnesota Medical School, Minneapolis, MN, 7Children's Hospital of Philadelphia, Philadelphia, PA, 8Childrens Hospital of Philadelphia, Philadelphia, PA, 9University of California San Francisco Benioff Children's Hospital, San Francisco, CA, 10Saint Jude Children's Research Hospital, Memphis, TN, 11Hematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada, 12Children's Oncology Group Statistics and Data Center, Monrovia, CA, 1314Hematology/Oncology, Riley Hospital for Children, Indianapolis, IN, 14CS Mott Children's Hospital, University of Michigan, Ann Arbor, MI, 15Department of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, 16S, S, MA, 17Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA
Purpose/Objective(s):
Outcomes for children with newly diagnosed high-risk neuroblastoma remain unsatisfactory. Current gains are mostly from later treatment phases, with induction disease control rates not significantly improving. 131I-MIBG has shown objective response rates up to 37% in patients with relapsed disease, and pilot studies support its feasibility in induction for newly diagnosed patients. Additionally, about 14% of tumors in high-risk patients have an anaplastic lymphoma kinase (ALK) aberration (activating mutation or amplification), which is associated with inferior survival. The third-generation ALK inhibitor lorlatinib is highly potent, effectively penetrates the blood-brain barrier, and overcomes resistance seen with earlier inhibitors.Materials/Methods:
ANBL1531 is a Phase 3 prospective study with a delayed three-arm randomization after one cycle of standard induction chemotherapy. Treatment is determined by tumor ALK status and central review of baseline 123I-MIBG scintigraphy. Patients with ALK-aberrant tumors are non-randomly assigned to receive lorlatinib added to a standard multimodal backbone (Arm E). Remaining patients with MIBG-avid disease are randomized 1:1 to receive either standard intensive therapy (Arm A) or standard therapy with the addition of a block of 131I-MIBG (15 mCi/kg) after the third induction cycle (Arm B). Patients with MIBG non-avid disease are non-randomly assigned to Arm D, which follows the Arm A backbone. All arms include definitive surgical resection, tandem autologous stem cell transplantation, and post-consolidation immunotherapy with dinutuximab, sargramostim, and isotretinoin. Radiotherapy-related protocol objectives include evaluating:- Standardization of Local Control: Delivering 21.6 Gy of external beam radiation therapy (EBRT) to the primary tumor bed post-tandem transplant, regardless of surgical resection extent.
- Metastatic Consolidation: Administering 21.6 Gy EBRT to up to five metastatic sites persistent on post-induction imaging.
- Patterns of Failure: Centrally reviewing recurrence imaging to define failure patterns and assess the impact of novel targeted therapies and standardized local control guidelines on recurrence patterns.
Results: TBD
Conclusion: TBD