Crizotinib in Pediatric ALK-Positive Anaplastic Large Cell Lymphoma and Inflammatory Myofibroblastic Tumors


Key Points

  • Response to crizotinib therapy was observed in 88% of patients with ALCL, with a complete response in 81%.
  • Response to crizotinib therapy was observed in 86% of patients with inflammatory myofibroblastic tumors, with a complete response in 36%.

In a Children’s Oncology Group study, high response rates were achieved with crizotinib (Xalkori) treatment in pediatric ALK-positive anaplastic large cell lymphomas (ALCL) and inflammatory myofibroblastic tumors. These results were reported by Mossé et al in the Journal of Clinical Oncology. ALK gene fusions are the primary genetic lesion underlying these pediatric tumors.

Study Details

The current report involved 26 patients with relapsed/refractory ALK-positive ALCL and 14 patients with metastatic or inoperable ALK-positive inflammatory myofibroblastic tumors from a phase I/II study who received oral crizotinib twice daily.

Response Rates

Response was observed among 5 of 6 patients (83%) with ALCL receiving crizotinib at 165 mg/m2 per dose and 18 of 20 patients (90%) receiving the recommended phase II dose of 280 mg/m2 per dose, with complete response observed in 5 (83%) and 16 (80%), respectively. Response was observed in 12 of 14 patients (86%) with inflammatory myofibroblastic tumors receiving 100, 165, or 280 mg/m2 per dose, with a complete response in 5 (36%). The remaining 1, 2, and 2 patients in the ALCL 165 mg/m2 and 280 mg/m2 groups and inflammatory myofibroblastic tumors group had stable disease as best response.

Initial evidence of response was observed by 4 weeks in 5 of the ALCL 165-mg/m 2 group, 13 of the ALCL 280-mg/m2 group, and 7 of the inflammatory myofibroblastic tumors group. The median duration of therapy was 2.79, 0.4, and 1.63 years in the 3 groups, respectively, with 12 patients stopping study therapy to undergo stem cell transplantation. Levels of NPM-ALK fusion transcripts decreased during treatment in most patients with ALCL.

Adverse Events

Grade 3 or 4 adverse events occurred in 83% and 100% of the ALCL dose groups and 71% of the inflammatory myofibroblastic tumors group. The most common grade 3 or 4 drug-related adverse event was decreased neutrophils, observed in 33% and 70% of the ALCL 165-mg/m2 and ALCL 280-mg/m2 groups and in 43% of the inflammatory myofibroblastic tumors group. Treatment was discontinued due to adverse events in two of the ALCL patients (neutropenia) and four of the inflammatory myofibroblastic tumors patients (neutropenia and lower extremity edema).

The investigators concluded: “The robust and sustained clinical responses to crizotinib therapy in patients with relapsed ALCL and metastatic or unresectable [inflammatory myofibroblastic tumors] highlight the importance of the ALK pathway in these diseases.”

The study was supported by the National Cancer Institute, Cookies for Kids Cancer Foundation, and Pfizer Inc.

Yael P. Mossé, MD, of Children’s Hospital of Philadelphia, University of Pennsylvania, is the corresponding author of the Journal of Clinical Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.