Complete remission with single agent lorlatinib in children with ALK+ anaplastic large cell lymphoma and central nervous system involvement: a case report

Therapies targeting cancer-specific mutations can result in remarkable clinical responses while reducing adverse effects. We describe the use of lorlatinib, a potent oral inhibitor of anaplastic lymphoma kinase (ALK) that crosses the blood brain barrier (BBB), in a case report of two patients with refractory and relapsed ALK+ anaplastic large cell lymphoma (ALK+ ALCL) with central nervous system (CNS) involvement. In both cases, treatment with single agent lorlatinib led to rapid and durable complete remission with tolerable side effects. Furthermore, we also describe a novel application of next generation sequencing to characterize circulating immune receptor DNA sequences associated with ALCL, and tracked the molecular response to therapy with subsequent blood specimens. These cases demonstrate that utilization of an effective targeted therapy against cancer-specific driver mutations that penetrates the BBB can lead to a significant clinical response, and presents clonal tracking for molecular response assessment as a potential approach for further study.