FDA Approves Crizotinib for Pediatric ALK+ ALCL Indication


Crizotinib—a tyrosine kinase inhibitor with activity against ALK, ROS1, and MET—was granted FDA approval for use in pediatric patients with relapsed or refractory ALK-positive anaplastic large cell lymphoma.

The FDA approved the multikinase inhibitor crizotinib (Xalkori) as therapy for young adult or pediatric patients who are at least 1 year of age with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is harboring an ALK aberration, according to the agent’s developer Pfizer.1

This marks the first time a biomarker-driven therapy earned an FDA indication for the treatment of this cancer. Crizotinib is currently indicated for the treatment of patients with metastatic ALK-positive or ROS1-positive non–small cell lung cancer (NSCLC), as detected by an FDA-approved test.

“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,” Yael Mossé, MD, who is an associate professor of pediatrics at the University of Pennsylvania/Children’s Hospital of Philadelphia as well as principal investigator for the pivotal study, said in a press release. “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 supplemental new drug application was supported by results from the ADVL0912 (NCT00939770) and A8081013 (NCT01121588) studies.

The phase 1/2 ADVL0912 trial examined pediatric patients with solid tumors or ALCL who were relapsed/refractory to known curative treatments to evaluate the antitumor activity and safety profile of twice daily crizotinib. Nine patients with ALK-translocated ALCL were enrolled, of whom 7 had a complete response and 1 had a partial response to therapy.2

In the phase 1b A8081013 trial, patients with ALK-positive advanced malignancies other than NSCLC were treated with twice daily crizotinib. Of the enrolled patients (n = 44), 17 with lymphoma experienced an objective response rate of 52.9%, comprised of 8 complete responses and 1 partial response. The progression-free survival rate at 2 years was 63.0% (95% CI, 35.3%-81.4%), which compared favorably with the frontline regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in ALK-positive ALCL. These data led the investigators to conclude that crizotinib could be a long-term treatment option for these patients as no other standard currently exists.

In both trials, crizotinib appeared to be well tolerated with gastrointestinal effects and visual disturbances occurring most frequently.

“Crizotinib represents an exciting new development in the treatment of this disease,” Meghan Gutierrez, chief executive officer at the Lymphoma Research Foundation, said in the release. “Researchers have made significant progress in our understanding of ALCL, which we hope will continue to improve treatment strategies and the options for children with ALCL. [This] news builds upon this progress and provides hope to pediatric patients with ALCL and their loved ones.”

ALCL is a form of non-Hodgkin lymphoma accounting for 10% to 15% of all childhood lymphomas, with roughly 90% of pediatric cases containing a chromosomal translocation that may include ALK.2 It is effectively treated in the frontline with intensive chemotherapy regimens, such as CHOP, but prognosis is poor if the disease relapses following chemotherapy.

Crizotinib previously received breakthrough therapy designation from the FDA for this indication in May 2018. The European Medicine Agency (EMA) has also agreed to a Paediatric Investigational Plan (PIP) for the use of crizotinib for this indication, which provides a path for potential regulatory submission in the European Union.


1. Pfizer’s Xalkori (crizotinib) approved by FDA for ALK-positive anaplastic large cell lymphoma in children and young adults. Pfizer. January 14, 2021. Accessed January 14, 2021. https://investors.pfizer.com/investor-news/press-release-details/2021/Pfizers-XALKORI-crizotinib-Approved-by-FDA-for-ALK-positive-Anaplastic-Large-Cell-Lymphoma-in-Children-and-Young-Adults/default.aspx

2. Mossé YP, Lim MS, Voss SD, et al. 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. 2013;14(6):472-480. doi: 10.1016/S1470-2045(13)70095-0

3. Gambacorti-Passerini C, Orlov S, Zhang L, et al. Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC): A phase 1b open-label study. Am J Hematol. 2018;93(5):607-614. doi: 10.1002/ajh.25043

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