Long-term remission of chronic-type adult T-cell leukemia/lymphoma associated with Graves’ disease treated with methimazole

Abstract

Adult T-cell leukemia/lymphoma (ATL) is a rare T-cell malignancy, where the chronic type often progresses to an acute form in the presence of poor prognostic factors. We report a remarkable case of chronic-type ATL that achieved long-term hematologic and molecular remission following methimazole treatment for concomitant Graves’ disease. A 58-year-old woman was diagnosed with chronic-type ATL in 2022. Her disease showed gradual progression with elevated soluble interleukin-2 receptor (sIL-2R) levels and lactate dehydrogenase. In 2023, she developed Sjögren’s syndrome and Graves’ disease. Following the initiation of methimazole for hyperthyroidism, her abnormal lymphocyte counts and sIL-2R levels unexpectedly and rapidly decreased. She has maintained clinical stability for over two years without any cytotoxic chemotherapy. Multi-color flow cytometry confirmed the disappearance of the CD4+/CADM1+/CD7− ATL cell population in the peripheral blood. Furthermore, longitudinal genomic profiling using Target-seq revealed a significant reduction in the variant allele frequencies of major driver clones, including a PDCD1 frameshift mutation, and a shift from monoclonal expansion to a polyclonal HTLV-1 carrier state. This case provides the first clinical evidence of a potential anti-ATL effect of methimazole and underscores the importance of the endocrine-immune axis in HTLV-1–associated malignancies, warranting further investigation into antithyroid therapy as a novel treatment strategy for indolent ATL.