Crizotinib in Combination With Chemotherapy for Pediatric Patients With ALK+ Anaplastic Large-Cell Lymphoma: The Results of Children's Oncology Group Trial ANHL12P1

Authors

Eric J. Lowe, Department of Pediatric Hematology-Oncology, Children's Hospital of the Kings Daughters, Norfolk, VA.
Anne F. Reilly, Department of Pediatrics, Perelman School of Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA.
Megan S. Lim, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Pennsylvania, PA.
Thomas G. Gross, Center for Cancer and Blood Disorders, Children's Hospital Colorado, University of Colorado School of Medicine, Denver, CO.
Lauren Saguilig, Children's Oncology Group, Monrovia, CA.
Donald A. Barkauskas, Department of Population and Public Health Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, CA.
Rui Wu, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Pennsylvania, PA.
Sarah Alexander, Division of Haematology/Oncology, Hospital for Sick Children, University of Toronto, Toronto, Canada.
Catherine M. Bollard, Department of Pediatrics, Center for Cancer and Immunology Research, Children's National Hospital and The George Washington University, Washington, DC.

Document Type

Journal Article

Publication Date

12-19-2022

Journal

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

DOI

10.1200/JCO.22.00272

Abstract

PURPOSE: Arm crizotinib (CZ) of the Children's Oncology Group trial ANHL12P1 (ClinicalTrials.gov identifier: NCT01979536) examined the efficacy and toxicity of adding CZ to standard chemotherapy for children with newly diagnosed, nonlocalized ALK+ CD30+ anaplastic large-cell lymphoma (ALCL). PATIENTS AND METHODS: Between 2013 and 2019, 66 enrolled children received CZ with chemotherapy. Patients received a 5-day prophase followed by six chemotherapy cycles at 21-day intervals with CZ administered twice daily during each 21-day cycle. The study was temporarily closed for two periods (total 12 months) to evaluate toxicity, during which CZ was discontinued. Measurements of fusion transcripts in peripheral blood were performed at diagnosis for minimal disseminated disease (MDD). RESULTS: The 2-year event-free survival (EFS) is 76.8% (95% CI, 68.5 to 88.1) and the 2-year overall survival is 95.2% (95% CI, 85.7 to 98.4). Fifteen patients relapsed and one patient died; median time to relapse was 7.4 months from diagnosis, with relapses occurring after chemotherapy was complete. The 66 patients completed 384 cycles of chemotherapy. Thirteen of the 66 patients experienced a grade 2+ thromboembolic adverse event (19.7%; 95% CI, 11.1 to 31.3). In the 25 patients who received mandated prophylactic anticoagulation, there were two thromboembolic events (8.0%; 95% CI, 0.01 to 26). Patients with negative MDD had a superior outcome, with an EFS of 85.6% (95% CI, 68.6 to 93.8); positive MDD was associated with a lower EFS of 58.1% (95% CI, 33.4 to 76.4). CONCLUSION: Arm CZ of ANHL12P1 demonstrated that the addition of CZ to standard treatment prevented relapses during therapy for children with ALCL, MDD predicted EFS, and the addition of CZ resulted in unexpected thromboembolic events. Overall survival and EFS rates are consistent with the highest reported outcomes for children with ALCL.

APA Citation

Lowe, Eric J.; Reilly, Anne F.; Lim, Megan S.; Gross, Thomas G.; Saguilig, Lauren; Barkauskas, Donald A.; Wu, Rui; Alexander, Sarah; and Bollard, Catherine M., "Crizotinib in Combination With Chemotherapy for Pediatric Patients With ALK+ Anaplastic Large-Cell Lymphoma: The Results of Children's Oncology Group Trial ANHL12P1" (2022). GW Authored Works. Paper 2078.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2078

Department

Pediatrics