Metachronous Presentation of BCL-2-Positive Lung Adenocarcinoma and Acute Myeloid Leukemia: A Case Presentation and Review of the Literature.

Introduction: The metachronous occurrence of epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma and acute myeloid leukemia (AML) presents significant clinical challenges. We explore the therapeutic implications of a shared molecular marker, BCL-2, in such a complex multiple primary malignancy scenario. Case Presentation: A female patient in her late 40s with Stage IVB EGFR L858R lung adenocarcinoma exhibiting high BCL-2 expression was treated with radiotherapy and icotinib. Seven months later, she developed AML with t(8;21). Initial AML therapy with a venetoclax-based regimen, selected partially due to the BCL-2 positivity, induced complete remission (CR). Upon AML relapse, a fast in vivo MiniPDX drug sensitivity assay guided the selection of a salvage combination therapy (Selinexor, Decitabine, and Venetoclax). Conclusion: This salvage regimen successfully induced a second CR in the refractory AML. This case highlights the complexity of managing these distinct malignancies, where the lung tumor's BCL-2 expression provided a rationale for the AML therapy. Furthermore, the MiniPDX assay proved valuable in guiding personalized therapy for refractory disease, demonstrating the potential of functional precision medicine strategies.