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

Eric J. Lowe, Anne F. Reilly, Megan S. Lim, Thomas G. Gross, Lauren Saguilig, Donald A. Barkauskas, Rui Wu, Sarah Alexander, Catherine M. Bollard

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 METHODSBetween 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 NPM-ALK fusion transcripts in peripheral blood were performed at diagnosis for minimal disseminated disease (MDD).RESULTSThe 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).CONCLUSIONArm 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.

Original languageEnglish
Pages (from-to)2043-2053
Number of pages11
JournalJournal of Clinical Oncology
Volume41
Issue number11
DOIs
StatePublished - 10 Apr 2023
Externally publishedYes

Fingerprint

Dive into the research topics of 'Crizotinib in Combination with Chemotherapy for Pediatric Patients with ALK+ Anaplastic Large-Cell Lymphoma: The Results of Children's Oncology Group Trial ANHL12P1'. Together they form a unique fingerprint.

Cite this