The addition of crizotinib (CZ) to a standard chemotherapy backbone for anaplastic large-cell lymphoma (ALCL) in children prevented on-therapy disease relapse but was associated with an unexpected increase in the number of thromboembolic events, according to research published in Journal of Clinical Oncology.
The findings are from arm CZ of the Children’s Oncology Group trial ANHL12P1 (ClinicalTrials.gov identifier: NCT01979536), which studied the efficacy and toxicity of adding CZ to standard chemotherapy for children with newly diagnosed, nonlocalized ALK+ CD30+ ALCL between 2013 and 2019. The primary endpoints were the occurrence of grade 3+ nonhematologic adverse events and event-free survival (EFS).
A total of 66 children (median age, 14 years; range, 6-20; 69% male and 31% female) were enrolled and received CZ with chemotherapy (5-day prophase followed by 6 21-day chemotherapy cycles with CZ administered twice daily).
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The study was temporarily closed for 2 periods to evaluate toxicity, totaling 12 months, and the risks of the study were updated to include thromboembolic events; during those periods, patients remained on study but were required to stop taking CZ.
The patients completed a total of 384 cycles of chemotherapy, with 94% of patients completing all 6 cycles. On February 8, 2019, the study met the stopping rule for thromboembolic events. Grade 2+ thromboembolic adverse events occurred in 13 of the 66 patients (19.7%; 95% CI, 11.1-31.3).
The study demonstrated a 2-year EFS rate of 76.8% (95% CI, 68.5-88.1) and a 2-year overall survival rate of 95.2% (95% CI, 85.7-98.4) among patients treated with CZ with chemotherapy.
Overall, 15 patients relapsed, and 1 patient died. The median time to relapse was 7.4 months from diagnosis, and nearly all relapses occurred after chemotherapy was complete (93%).
“Given the increased rate of thromboembolic events associated with CZ, it is unlikely to be preferred over brentuximab given on the chemotherapy backbone used in this trial,” the study authors wrote in their report. “CZ’s activity in ALCL does warrant consideration for use in frontline ALCL potentially in combination with brentuximab alone, rather than as part of a multiagent chemotherapy regimen.”
Limitations of the study included lack of central review of pathologic specimens and subtype classification for most patients on the trial.
Disclosure: One study author declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures.
Reference
Lowe EJ, Reilly AF, Lim MS, et al. Crizotinib in combination with chemotherapy for pediatric patients with ALK+ anaplastic large-cell lymphoma: The results of Children’s Oncology Group trial ANHL12P1. J Clin Oncol. 2023;41(11):2043-2053. doi:10.1200/JCO.22.00272
