HGG-08. Lorlatinib for the treatment of ALK fusion positive infant high grade glioma

Abstract

BACKGROUND: High grade gliomas (HGG) are very rare in the infant age group with approximately 800 cases diagnosed in the USA and Europe each year. Histologically, HGG in infants resemble HGG in older children and adults but have distinct molecular features like ALK, NTRK, MET and ROS1 fusions. HGG in infants have superior outcomes compared to older age groups (5-year overall survival >50%) when treated with a radiation sparing regimen. Here we present the unique treatment course for an infant with ALK fusion positive HGG, including molecularly targeted therapy. CASE DESCRIPTION: A 3-month-old African-American female presented with acute onset vomiting, right facial droop and focal seizures. MRI of the brain revealed a right frontal intraparenchymal mass. Upfront gross total resection (GTR) was performed and histologic diagnosis of epithelioid glioblastoma was made. The molecular analysis of the tumor showed ZNF397-ALK fusion. The patient was treated with a radiation sparing regimen consisting of Carboplatin 8 mg/kg x 2 days and Etoposide 3 mg/kg x 3 days for 6 cycles. The patient tolerated the chemotherapy and had no evidence of disease recurrence at the completion of chemotherapy. However, 8 months after completion of therapy, she had a localized relapse and underwent a second GTR. Repeat molecular analysis confirmed the presence of ZNF 397-ALK fusion. She was started on Lorlatinib at 95 mg/m2/day once a day. She continued on the medication for 15 months and had no evidence of disease at the end of 15 months. During the course of her treatment, she had excessive weight gain (CTCAE grade-3) despite dose reduction. CONCLUSION: Infant high grade gliomas have a high prevalence of gene fusions including ALK fusions. This case shows that these fusions may be amenable to molecularly targeted treatments and should be studied in prospective clinical trials.