The Role of the Lymphocyte Transformation Test in Immune-Related Adverse Events from Immune Checkpoint Inhibitors: A Case Series

<b>Background</b>: Immune-related adverse events (irAEs) represent a considerable complication associated with the use of immune checkpoint inhibitors (ICIs) in oncology patients. Assessing causality is particularly challenging in patients administered multiple therapeutic agents. The Lymphocyte Transformation Test (LTT) may aid in causality analysis, although its clinical utility remains investigational. <b>Objectives</b>: To evaluate the potential utility of the Lymphocyte Transformation Test (LTT) in the causality analysis of irAEs in cancer patients and to assist clinicians in the decision-making process regarding ICI rechallenge. <b>Methodology</b>: We present a case series of seventeen cancer patients who developed irAEs during ICI therapy. Causality was assessed using the Spanish Pharmacovigilance System, and LTT was performed for both ICIs and co-medications. <b>Results</b>: Events primarily affect hepatic, respiratory, and renal functions. Five patients showed a positive LTT to ICIs (range 3.9-13.6), all with high-grade irAEs, and none underwent rechallenge. Six patients were positive for concomitant drugs: three tested positive for both. The initial high-grade irAEs rate was 53.9%. After rechallenging, 81.8% had all-grade and 45.5% had high-grade irAEs, predominantly pneumonitis. <b>Conclusions</b>: LTT may provide supportive evidence in complex irAE cases and assist clinicians in decision-making regarding ICI rechallenge. More prospective studies are needed.