Crizotinib Produced Robust Response in ALK-Positive Pediatric Lymphoma

Pediatric patients with ALK-positive anaplastic large cell lymphomas (ALCL) and inflammatory myofibroblastic tumors (IMT) had strong responses to treatment with the ALK-targeting drug crizotinib, according to the results of a small study from the Children’s Oncology Group.

“The robust and sustained clinical responses to crizotinib in patients with relapsed or refractory ALK-driven ALCL and IMT highlight the importance of this oncogene and the sensitivity to ALK inhibition in these diseases,” wrote Yael P. Mossé, MD, of Children’s Hospital of Philadelphia, and colleagues in the Journal of Clinical Oncology.

According to the study, ALCLs, a subset of peripheral T-cell lymphoma, account for about 15% of all childhood lymphomas, and the majority of them have the ALK gene fusion. Similarly, ALK gene translocations have been described in about one-half of IMTs.

This trial built on phase I results that showed that crizotinib was well tolerated in children at a dose up to 280 mg/m². The trial included 26 patients with relapsed or refractory ALK-positive ALCL and 14 patients with metastatic or inoperable ALK-positive IMT. All patients received crizotinib twice daily.

Overall response rates were good for patients with both diseases. For ALCL, patients treated with doses of 165 and 280 mg/m² had an overall response rate of 83% and 90%, respectively. Patients with IMT treated at 100, 165, and 280 mg/m² had overall response rates of 86%.

“The rate, type, and duration of response vastly exceeded those typically observed in any early-phase clinical trial for children with relapsed/refractory cancer, possibly owing to the less complex genomic landscape of ALCL and the addiction to a single driver oncogene,” the researchers wrote.

Complete responses occurred in 83% of ALCL patients treated at the 165 mg/m² dose and 80% of ALCL patients treated at the 280 mg/m² dose. A little more than one-third (36%) of patients with IMT had a complete response and one-half had a partial response. Among the twelve patients with IMT who responded, seven responded within 4 weeks, two within 8 weeks, and three within 20 weeks of starting therapy.

A decrease in neutrophil count was the most common drug-related adverse event, occurring in 33% and 70% of ALCL patients treated at the 165 and 280 mg/m² doses, and 43% of patients with IMT.

“Notably, the onset and durability of responses do not seem to be dose dependent, with objective and sustained responses seen at the lower (165 mg/m²) and higher (280 mg/m²) dosing of crizotinib in ALCL,” the researchers wrote. “The robust and sustained activity observed in this trial has provided the rationale for the currently accruing COG pilot phase II study (NCT01979536) combining crizotinib at 165 mg/m² with conventional chemotherapy in newly diagnosed patients with ALCL.”