Severe Psychosis Associated With Lorlatinib

Lorlatinib is a third-generation ALK tyrosine kinase inhibitor (TKI) that has been specifically designed to counteract resistance mutations of previous ALK TKIs. 1 Basit S. Ashraf Z. Lee K. Latif M. First macrocyclic 3(rd)-generation ALK inhibitor for treatment of ALK/ROS1 cancer: clinical and designing strategy update of lorlatinib. Eur J Med Chem. 2017; 134: 348-356 Crossref PubMed Scopus (77) Google Scholar This drug has been engineered to effectively traverse the blood-brain barrier and treat recurrent brain metastases. However, lorlatinib treatment has been associated with various neurocognitive, mood, psychotic, and speech adverse effects (AEs), 2 Dagogo-Jack I. Abbattista A. Murphy J.F. et al. Factors associated with developing neurocognitive adverse events in patients receiving lorlatinib after progression on other targeted therapies. J Thorac Oncol. 2023; 18: 67-78 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar which were not reported with earlier generations of ALK TKIs. Although most of these neurocognitive AEs are mild (grade 1–2) 3 Mazieres J. Iadeluca L. Shaw A.T. et al. Patient-reported outcomes from the randomized phase 3 crown study of first-line lorlatinib versus crizotinib in advanced ALK-positive non-small cell lung cancer. Lung Cancer. 2022; 174: 146-156 Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar and resolve after discontinuing the drug, 2 Dagogo-Jack I. Abbattista A. Murphy J.F. et al. Factors associated with developing neurocognitive adverse events in patients receiving lorlatinib after progression on other targeted therapies. J Thorac Oncol. 2023; 18: 67-78 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar the present case exhibited a severe lorlatinib-induced psychosis. Factors Associated With Developing Neurocognitive Adverse Events in Patients Receiving Lorlatinib After Progression on Other Targeted TherapiesJournal of Thoracic OncologyVol. 18Issue 1PreviewThe safety profile of lorlatinib includes neurocognitive adverse events (NAEs). Baseline factors associated with developing NAEs remain poorly characterized. Full-Text PDF Open Access