Anaplastic Large Cell Lymphoma: Crizotinib Approved for Younger Patients

ALK in complex with crizotinib.

Crizotinib (Xalkori®, Pfizer) is now FDA approved for the treatment of pediatric patients age one year and older and young adult patients with relapsed/refractory systemic ALK-positive anaplastic large cell lymphoma (ALCL).

The approval was based on Study ADVL0912 (NCT00939770), a single-arm phase 1/2 trial. “Various human cancers have ALK gene translocations, amplifications, or oncogenic mutations, such as ALCL, inflammatory myofibroblastic tumors, non-small cell lung cancer (NSCLC), and neuroblastoma” wrote the investigators, led by first author Yael P. Mossé, MD, Associate Professor of Pediatrics at the University of Pennsylvania Perelman School of Medicine, in their publication in Lancet Oncology in 2013. “Therefore, ALK inhibition could be a useful therapeutic strategy in children.”

The trial enrolled 79 patients, 26 of whom had relapsed/refractory systemic ALK-positive ALCL. Eligible patients were between one and 21 years of age and had received at least one prior systemic therapy. Patients received crizotinib in a dose of either 280 mg/m2 or 165 mg/m2 orally twice daily until disease progression or unacceptable toxicity. Treatment discontinuation was permitted if patients underwent hematopoietic stem cell transplantation (HSCT).

Crizotinib produced an overall response rate of 88% and a complete remission rate of 81%. Among those who experienced a response, the response was maintained for at least six months in 39% of patients and for at least 12 months in 22% of patients.

The most common adverse events occurring in at least 35% of patients included diarrhea, vomiting, nausea, vision disorder, headache, musculoskeletal pain, stomatitis, fatigue, decreased appetite, pyrexia, abdominal pain, cough, and pruritus, with high rates of gastrointestinal toxicity (92%) and grade 1/2 ocular toxicity (65%). Grade 3/4 laboratory abnormalities experienced by at least 15% of patients included neutropenia, lymphopenia, and thrombocytopenia. Serious adverse reactions, including neutropenia and infection, occurred in 35% of patients.

Antiemetics should be administered to patients both before and during treatment with crizotinib. Additionally, ophthalmologic evaluations and monthly assessments of visual symptoms and acuity should be performed in order to manage the risk of visual loss.

“With increased attention being placed on the development of targeted agents and the importance of ALK in pediatric patients with ALCL, the approval of crizotinib is a significant victory in our ongoing fight against these cancers that provides an outpatient oral medication with the real possibility of robust and sustained responses,” commented Dr. Mossé. “ALK fusions play an important role in the pathology of ALCL, and it’s exciting that crizotinib is able to leverage this dependence to provide a treatment option for young people faced with ALCL disease progression.”

The recommended dose of crizotinib is 280 mg/m2 orally twice daily based on body surface area.

For More Information

Mossé YP, Lim MS, Voss SD, et al (2013). Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children’s Oncology Group phase 1 consortium study. Lancet Oncol, 14(6):472-480. DOI:10.1016/S1470-2045(13)70095-0 (2020). Crizotinib in treating younger patients with relapsed or refractory solid tumors or anaplastic large cell lymphoma. NLM identifier: NCT00939770.

Xalkori® (crizotinib) prescribing information (2020). Pfizer. Available at:

US Food & Drug Administration (2021). FDA approves crizotinib for children and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma. Available at:

Image credit: M. McTigue, Y. Deng, W. Liu, and A. Brooun. Courtesy of the Research Collaboratory for Structural Bioinformatics, Protein Data Bank

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