Abstract
Crizotinib has an overall response rate of 90% in ALCL and 86% in IMT at the recommended phase II dose.
Major finding: Crizotinib has an overall response rate of 90% in ALCL and 86% in IMT at the recommended phase II dose.
Concept: Crizotinib reduced the levels of NPM–ALK in the majority of patients with ALCL.
Impact: Crizotinib may be effective for the treatment of patients with ALK fusion–positive ALCL or IMT.
Chromosomal translocations that result in oncogenic activation of the receptor tyrosine kinase ALK are common in patients with pediatric anaplastic large cell lymphomas (ALCL) and inflammatory myofibroblastic tumors (IMT), suggesting the possibility for therapeutic targeting of ALK. The ALK–ROS1–MET small-molecule inhibitor crizotinib was approved to treat patients with non–small cell lung cancer harboring ALK fusions. Mossé and colleagues aimed to evaluate the activity of crizotinib in patients with ALK fusion–positive relapsed or refractory ALCL or IMT. A total of 26 patients with ALCL and 14 patients with IMT were enrolled and treated with crizotinib. The primary objectives were to assess the efficacy and safety of crizotinib, and secondary objectives included exploring the relationship between clinical response to crizotinib and serial detection of NPM–ALK fusion transcripts in patients with ALCL. The patients with ALCL were treated with either 165mg/m2 crizotinib (ALCL165; 6 patients) or the recommended phase II dose of 280mg/m2 (ALCL280; 20 patients). The patients with IMT were treated with 100mg/m2 (1 patient), 165mg/m2 (1 patient), or 280mg/m2 (12 patients), and the doses exhibited similar toxicity and responses. The overall response rate was 83% in ALCL265 patients, with 5 of 6 patients achieving complete responses; 90% in ALCL280 patients, with 16 of 20 patients achieving complete responses and 2 achieving partial responses; and 86% in patients with IMT, with 5 of 14 patients achieving complete responses and 7 achieving partial responses. Further, levels of NPM–ALK decreased throughout crizotinib therapy in most patients with ALCL. Grade 3 or 4 adverse events occurred in 83% of patients, with the most common being decreased neutrophil count. Collectively, these findings demonstrate that crizotinib achieves responses in patients with relapsed or refractory ALK-driven ALCL or IMT, supporting further clinical investigation.
Note: Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/content/early/by/section.
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