NPM1-ALK I1171T

He achieved complete remission after 2 cycles with multi-agent chemotherapy (dexamethasone, ifosfamide, methotrexate, cytarabine, etoposide, cyclophosphamide, doxorubicin and brentuximab)...He had progressive disease after 3 weeks and was changed to combination chemotherapy with brentuximab and nivolumab with the addition of alectinib, a second generation ALK inhibitor. He again had progressive disease within 3 weeks and received therapy with ifosfamide, carboplatin and etoposide with a mixed response...Based on preclinical studies and limited clinical studies demonstrating that ALKI1171T mutations are resistant to crizotinib and alectinib but may maintain sensitivity to ceritinib, the patient started ceritinib in combination with brentuximab... Testing for the presence of ALK rearrangements via IHC is standard in pediatric ALCL but cannot solely predict sensitivity to specific inhibitors. Consideration should be made for upfront ALK gene sequencing as this may drive therapeutic decisions regarding which inhibitor is most likely to result in a clinical response.