Safe Treatment of an Extensive-Stage Small-Cell Lung Cancer With Tarlatamab in an Orthotopic Heart Transplantation Patient: A Case Report

Graft rejection is the major challenge that solid organ transplant recipients face. As a consequence, lung cancer patients of this population have been consistently excluded from clinical trials involving the use of immunotherapy agents due to the increased risk of graft rejection. Tarlatamab is a novel bi-specific T-cell recruiter monoclonal antibody targeting delta-like ligand 3 (DLL3) on cancer cells and CD3 on T-cells; hence, it is theoretically much safer than other checkpoint inhibitor immunotherapy agents that boost T-cells non-specifically. Tarlatamab received Food and Drug Administration (FDA) approval in 2024 for the treatment of adults with extensive-stage small-cell lung cancer (ES-SCLC) that has progressed on or after platinum-based chemotherapy. Here, we report safe treatment of an extensive-stage small-cell lung cancer patient with an orthotopic heart transplant with tarlatamab. The patient received four doses between April and June 2025 without evidence of graft rejection or dysfunction. As of August 2025, the patient continues treatment without any adverse events.