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FDA Approves Crizotinib for Children and Young Adults With Relapsed or Refractory Systemic ALK-Positive ALCL


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On January 14, the U.S. Food and Drug Administration (FDA) approved crizotinib (Xalkori) for pediatric patients aged 1 year and older and young adults with relapsed or refractory systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive. The safety and efficacy of crizotinib have not been established in older adults with relapsed or refractory systemic ALK-positive ALCL.

Study ADVL0912

Efficacy was evaluated in Study ADVL0912, a multicenter, single-arm, open-label trial in patients aged 1 to ≤ 21 years. The study included 26 patients with relapsed or refractory systemic ALK-positive ALCL who had received at least one systemic treatment. Patients received crizotinib at 280 mg/m(n = 20) or 165 mg/m2 (n = 6) orally twice daily until disease progression or unacceptable toxicity. Patients were permitted to discontinue crizotinib to undergo hematopoietic stem cell transplantation.

Efficacy was based on objective response rate and duration of response as assessed by an independent review committee. The objective response rate in the 26 patients was 88% (95% confidence interval [CI] = 71%–96%), with a complete remission rate of 81%. Of the 23 patients who achieved a response, 39% maintained response for at least 6 months and 22% maintained response for at least 12 months.

Ocular toxicity (grade 1 or 2 visual disorders) occurred in 65% of patients with ALCL; gastrointestinal toxicity occurred in 92%; and serious adverse reactions occurred in 35%, most often from neutropenia and infection. The most common adverse reactions (≥ 35%), excluding laboratory abnormalities, were diarrhea, vomiting, nausea, vision disorder, headache, musculoskeletal pain, stomatitis, fatigue, decreased appetite, pyrexia, abdominal pain, cough, and pruritus. Grade 3–4 laboratory abnormalities (≥ 15%) were neutropenia, lymphopenia, and thrombocytopenia.

The recommended crizotinib dosage for patients with systemic ALCL is 280 mg/m2 orally twice daily based on body surface area. Antiemetics are recommended prior to and during treatment with crizotinib in patients with ALCL. Due to the risk of visual loss, ophthalmologic evaluations are recommended at baseline and serially thereafter, coupled with monthly assessments of visual acuity and visual symptoms.


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