Targeting ALK With Crizotinib in Pediatric Anaplastic Large Cell Lymphoma and Inflammatory Myofibroblastic Tumor: A Children's Oncology Group Study.
Fiche publication
Date publication
octobre 2017
Journal
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ROLLAND Delphine
Tous les auteurs :
Mossé YP, Voss SD, Lim MS, Rolland D, Minard CG, Fox E, Adamson P, Wilner K, Blaney SM, Weigel BJ
Lien Pubmed
Résumé
Purpose Fusions involving the ALK gene are the predominant genetic lesion underlying pediatric anaplastic large cell lymphomas (ALCL) and inflammatory myofibroblastic tumors (IMTs). We assessed the activity of the ALK inhibitor crizotinib in patients who had no known curative treatment options at diagnosis or with relapsed/recurrent disease. Methods In this study, 26 patients with relapsed/refractory ALK-positive ALCL and 14 patients with metastatic or inoperable ALK-positive IMT received crizotinib orally twice daily. Study objectives were measurement of efficacy and safety. Correlative studies evaluated the serial detection of NPM-ALK fusion transcripts in patients with ALCL. Results The overall response rates for patients with ALCL treated at doses of 165 (ALCL165) and 280 (ALCL280) mg/m were 83% and 90%, respectively. The overall response rate for patients with IMT (treated at 100, 165, and 280 mg/m/dose) was 86%. A complete response was observed in 83% (five of six) of ALCL165, 80% (16 of 20) of ALCL280, and 36% (five of 14) of patients with IMT. Partial response rates were 0% (none of six), 10% (two of 20), and 50% (seven of 14), respectively. The median duration of therapy was 2.79, 0.4, and 1.63 years, respectively, with 12 patients ceasing protocol therapy to proceed to transplantation. The most common drug-related adverse event was decrease in neutrophil count in 33% and 70% of the ALCL165 and ALCL280 groups, respectively, and in 43% of patients with IMT. Levels of NPM-ALK decreased during therapy in most patients with ALCL. Conclusion The robust and sustained clinical responses to crizotinib therapy in patients with relapsed ALCL and metastatic or unresectable IMT highlight the importance of the ALK pathway in these diseases.
Mots clés
Adolescent, Anaplastic Lymphoma Kinase, Child, Child, Preschool, Crizotinib, Dose-Response Relationship, Drug, Female, Humans, Lymphoma, Large-Cell, Anaplastic, drug therapy, Male, Molecular Targeted Therapy, Neoplasm Recurrence, Local, drug therapy, Neoplasms, Muscle Tissue, drug therapy, Protein Kinase Inhibitors, administration & dosage, Pyrazoles, administration & dosage, Pyridines, administration & dosage, Receptor Protein-Tyrosine Kinases, antagonists & inhibitors
Référence
J Clin Oncol. 2017 Oct 1;35(28):3215-3221