Efficacy and safety of crizotinib in ALK-positive systemic anaplastic large-cell lymphoma in children, adolescents, and adult patients: results of the French AcSé-crizotinib trial

Background: The French phase II AcSé-crizotinib trial aimed to evaluate the safety and efficacy of crizotinib in patients with ALK, ROS1, and MET-driven malignancies, including ALK-positive anaplastic large-cell lymphoma (ALK⁺ ALCL). Methods: ALK⁺ ALCL patients 12 months or older with measurable disease and no standard care options available received crizotinib twice daily at 165 mg/m² in children and adolescents and 250 mg in adults. The primary end-point was the response rate at 8 weeks. Results: Twenty-eight patients were enroled between February 2014 and March 2018. Three patients who were not treated were excluded from the analysis. The median age was 19 years. The median previous line of chemotherapy was two. In the 24 patients with an evaluable response, the response rate at 8 weeks was 67% (95% CI: 47–82%). All patients discontinued crizotinib after a median treatment duration of 3.7 months: eight for progression, two for adverse events (AEs) related to prior treatments, and 15 by choice, including six for allogeneic stem-cell transplantation. The median follow-up was 45 months. Nine patients experienced an event: eight relapses (seven after crizotinib discontinuation and one after dose reduction), and one died in complete remission. The median duration of response was 43.3 months (95% CI: 8.3–not reached). The 3-year progression-free and overall survival rates were 40% (95% CI: 23–59%) and 63% (95% CI: 43–79%). Grade 3 or 4 treatment-related AEs occurred in 32% of patients. Conclusion: Crizotinib shows efficacy and an acceptable safety profile in ALK⁺ ALCL relapsed/refractory patients. However, a large proportion of patients experience a relapse after crizotinib discontinuation. Future studies will assess if prolonged ALK inhibitor exposure has curative potential without consolidation.