From the Research
Lorlatinib is a highly effective treatment option for patients with ALK-driven neuroblastoma, particularly those with relapsed or refractory disease, and should be considered as a first-line treatment in these cases. The most recent and highest quality study, published in 2024 1, demonstrates the long-lasting response to lorlatinib in patients with ALK-driven relapsed or refractory neuroblastoma, with some patients experiencing durable responses of up to 5 years. This study also highlights the potential of targeted circulating tumor DNA (ctDNA) analysis as a guide for treatment decisions in these patients.
Key Findings
- Lorlatinib has shown efficacy in treating neuroblastoma with ALK mutations, amplifications, or rearrangements 2, 3, 1
- The typical dosing for children with neuroblastoma is weight-based, approximately 95-100 mg/m² once daily, though specific dosing should be determined by an oncologist based on the patient's characteristics 2
- Treatment duration is typically continuous until disease progression or unacceptable toxicity 2
- Lorlatinib has demonstrated improved central nervous system penetration compared to earlier ALK inhibitors, making it particularly valuable for patients with CNS involvement 4, 3
- Common side effects include hypercholesterolemia, edema, weight gain, peripheral neuropathy, and cognitive effects, which require regular monitoring 2, 3
Recommendations
- Genetic testing for ALK alterations is essential before initiating therapy, as lorlatinib is only effective in ALK-positive cases 4, 2, 3, 1
- Lorlatinib should be considered as a first-line treatment option for patients with ALK-driven neuroblastoma, particularly those with relapsed or refractory disease 1
- Targeted ctDNA analysis may be useful for evaluating treatment response and detecting early signs of relapse in patients with ALK-driven neuroblastoma 1