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

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). 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 endpoint was the response rate at 8 weeks. Twenty-eight patients were enrolled between 02/2014 and 03/2018. Three patients, not treated, were excluded from analysis. Median age was 19 years. Median previous line of chemotherapy was two. In the 24 patients with 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: 8 for progression, 2 for adverse events related to prior treatments, and 15 by choice including 6 for allogenic 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 adverse events occurred in 32% of patients. 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. •High response rate is obtained with crizotinib in relapsed/resistant ALK+ ALCL.•Drug level monitoring should be an inherent part of crizotinib standard of care.•Relapse after discontinuing crizotinib or after a dose reduction are not rare.•Optimal dose and duration of crizotinib as well as the need for a consolidation have to be determined.