COG ADVL0912: crizotinib in children with ALK-driven tumours

Fusions of the ALK gene drive most paediatric anaplastic large cell lymphomas and inflammatory myofibroblastic tumours. This Children's Oncology Group phase 1/2 study gave crizotinib, the ALK inhibitor developed for lung cancer, to children with relapsed or refractory solid tumours or ALCL; the registry records 122 participants across all its cohorts. The 2017 report covers 26 patients with relapsed or refractory ALK-positive ALCL and 14 with metastatic or inoperable ALK-positive inflammatory myofibroblastic tumour.

In ALCL the overall response was 83 per cent at 165 mg/m2 and 90 per cent at 280 mg/m2, with complete responses in five of six and 16 of 20. The median duration of therapy was 2.79 and 0.4 years, and 12 patients stopped protocol therapy to proceed to transplant. The commonest drug-related adverse event was a fall in the neutrophil count, in 33 and 70 per cent of the two ALCL dose groups. Levels of the NPM-ALK fusion transcript in the blood fell during treatment in most patients with ALCL.