On January 14, 2021, the FDA approved crizotinib (Xalkori; Pfizer) for the treatment of young patients aged 1 to 21 years with relapsed or refractory systemic anaplastic large-cell lymphoma (ALCL) and ALK mutation. The safety and efficacy of crizotinib have not been established in older adults with this diagnosis. The FDA granted this application priority review and breakthrough therapy and orphan drug designations.
Crizotinib was previously approved for patients with metastatic non–small-lung cancer and ALK or ROS1 mutation.
This new indication for crizotinib was based on data from the ADVL0912 study, a multicenter, single-arm, open-label clinical trial in patients aged 1 to 21 years. A total of 26 patients with relapsed or refractory ALCL and ALK mutation were enrolled in the study. All patients had previously received at least 1 systemic treatment.
In the ADVL0912 study, 20 patients received oral crizotinib 280 mg/m2 and the other 6 patients received 165 mg/m2 twice daily until disease progression or until unacceptable adverse events. The patients were permitted to discontinue crizotinib therapy so they could undergo hematopoietic stem-cell transplant.
The study efficacy was based on the objective response rate (ORR) and the duration of response (DOR), as assessed by an independent review committee. The ORR in the 26 patients was 88% (95% confidence interval, 71-96), with an 81% rate of complete remission. Of the 23 patients who achieved a response, 39% of patients had a DOR of ≥6 months, and 22% had a DOR of ≥12 months.
Grade 1 or 2 ocular adverse events were reported in 65% of patients with ALCL; gastrointestinal adverse events were reported in 92% of the patients, and serious adverse reactions occurred in 35% of the patients, most often from neutropenia and infection. Grade 3 or 4 laboratory abnormalities (≥15%) included neutropenia, lymphopenia, and thrombocytopenia.
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.