FDA Approves Crizotinib for Young Patients With Relapsed/Refractory, ALK+ ALCL
On January 14, 2021, the FDA approved crizotinib (Xalkori; Pfizer) for the treatment of young adults and pediatric patients aged ≥1 year with relapsed or refractory, systemic, ALK-positive anaplastic large-cell lymphoma (ALCL). The application for this approval was granted priority review, breakthrough designation, and orphan drug designation by the FDA.
This approval was based on efficacy data from Study ADVL0912, a single-arm, multi-center, open-label clinical trial of 26 patients aged 1 to 21 years with relapsed or refractory, systemic, ALK-positive ALCL who had received at least 1 systemic treatment.
Patients in the study were given crizotinib 280 mg/m2 (n = 20) or 165 mg/m2 (n = 6) twice daily until disease progression or unacceptable toxicity occurred, and could discontinue crizotinib to undergo hematopoietic stem cell transplantation.
The efficacy of the therapy was based on objective response rate (ORR) and duration of response according to independent committee review. Among 26 patients, the ORR was 88% (95% CI, 71-96), with a complete remission rate of 81%. Of the 23 patients who achieved a response, 39% and 22% maintained their responses for at least 6 and 12 months, respectively.
The most common (≥35%) adverse reactions (excluding laboratory abnormalities) were diarrhea, vomiting, nausea, vision disorder, headache, musculoskeletal pain, stomatitis, fatigue, decreased appetite, pyrexia, abdominal pain, cough, and pruritus.
Ocular toxicity was documented in 65% of patients with ALCL, gastrointestinal toxicity occurred in 92%, and serious adverse reactions occurred in 35% (mostly neutropenia and infection). Neutropenia, lymphopenia, and thrombocytopenia were reported as grade 3-4 laboratory abnormalities occurring in ≥15% patients .
Of note, the safety and efficacy of crizotinib has not been established in older adults with relapsed or refractory, systemic, ALK-positive ALCL.—Hina M. Porcelli
Source: US Food and Drug Administration. FDA approves crizotinib for children and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma. Updated January 15, 2020. www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-crizotinib-children-and-young-adults-relapsed-or-refractory-systemic-anaplastic-large. Accessed January 15, 2020.