Advanced thymic carcinoma responds to venetoclax and azacitidine

Clinical Practice Points • Thymic carcinoma is a rare, aggressive malignancy with limited systemic treatment options beyond platinum-based chemotherapy. Responses to chemotherapy, immunotherapy, and subsequent lines of therapy are often short-lived, and there are no well-established targeted therapies. The anti-apoptotic protein BCL-2 is frequently expressed in thymic carcinomas, but BCL-2 directed therapy is not part of current standard management. Venetoclax in combination with azacitidine is an established, well-tolerated regimen for older or unfit patients with acute myeloid leukemia (AML), where it enhances apoptosis through BCL-2 inhibition and epigenetic modulation. • In this heavily pretreated patient with advanced thymic carcinoma who developed therapy-related AML, venetoclax plus azacitidine induced not only to hematologic remission of AML but also marked metabolic and radiologic regression of metastatic thymic carcinoma, accompanied by symptomatic improvement. The tumor demonstrated diffuse BCL-2 expression on immunohistochemistry, supporting a biologically plausible mechanism of response. • This case adds to the limited emerging evidence that BCL-2 blockade, particularly in combination with hypomethylating agents, may have clinically meaningful activity in thymic epithelial malignancies. These findings identify BCL-2 as a potential therapeutic target in thymic carcinoma and suggests that venetoclax-based regimens could be explored as a therapeutic strategy in selected patients, particularly those with BCL-2 expressing tumors or limited standard options. This case also supports prospective investigation of BCL-2 directed strategies in thymic epithelial tumors and highlights the value of biomarker driven treatment even in rare thoracic cancers.