Treatment and Outcome of ATL Diagnosed in 2021 to 2023 By the Kagoshima ATL Registry

Introduction: Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy with very poor prognosis. We have initiated a all-case registration of ATL patients (Kagoshima ATL registry) to reveal the epidemiology, clinical profile and prognosis of ATL by constructing a database of ATL patients diagnosed in Kagoshima, Japan, one of the most pandemic areas for ATL in the world. Methods: We prospectively collected clinical information in newly diagnosed patients with ATL on or after April 1, 2021 at all facilities in Kagoshima Prefecture providing hematology services. The follow-up data in registered patients was then collected annually. This study was approved by the ethics committee of each institution. Results and Discussion; A total of 167 patients were registered during the period of April 1, 2021 to March 31, 2023, of which 161 patients were included in this analysis by excluding 3 patients who were not met the criteria of registration and 3 patients who had duplicated registration. The number of patients was 83, 52, 15, and 13 in acute, lymphoma, chronic, and smoldering types, respectively. In 161 cases, aggressive ATL (acute- and lymphoma-type, and chronic-type with unfavorable prognostic factors) and indolent ATL (smoldering-type and chronic-type without any unfavorable prognostic factors) was 143 cases, 18 cases, respectively. The median age of onset was 72 years old. The median observation period was 19.8 (0.6-35) months, and the median survival was 6.8, 11.6 months, not-reached, and not-reached for acute, lymphoma, chronic, and smoldering types, respectively. Survival stratification by the simplified ATL-prognostic index (sATL-PI) at diagnosis and the Japan Clinical Oncology Group (JCOG)-PI for acute and lymphoma-type ATL, and aggressive ATL were confirmed, respectively (P<0.0001). In aggressive ATL, 83.9 % (120/143) of patients received first-line treatment. Among them, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone), VCAP-AMP-VECP (VCAP: vincristine, cyclophosphamide, doxorubicin, and prednisolone, AMP: doxorubicin, ranimustine, and prednisolone, and VECP: vindesine, etoposide, carboplatin, and prednisolone), any chemotherapy by cytotoxic agents combined with mogamulizumab (Moga+CTx), and CHP therapy combined with brentuximab vedotin (BV-CHP) were performed in 30.0 %, 28.3 %, 28.3 %, and 13.4% of patients, respectively. Allogeneic stem cell transplantation (Allo-HSCT) was performed in 11.2% (16/143) patients with aggressive ATL with a median age of 62.5 years (44-72 years). Allo-HSCT was performed in 25.9 % (15/58) of patients who were equal or younger than 70 years old at diagnosis. In 34 patients who received Moga+CTx and 16 patients who received BV-CHP in the first-line therapy, 94.1% and 68.7% of patients acquired CR or PR, respectively (P=0.073). The time to next treatment in patients who received Moga+CTx and BV-CHP were 8.1 and 3.2 months, respectively (P=0.0231), indicating that the remission by Moga+CTx was more durable than the BV-CHP in the first-line treatment. Second-line treatment was applied to 81 patients. BV or Moga with or without CTx were most frequently used in the second-line treatment (n=81). This registration is expected to provide real-world data of ATL by regional registry in one of the world's most endemic area in HTLV-1 under the circumstances of the decreasing of HTLV-1 infected individuals in younger people and recent introduction of novel therapeutic agents including tucidinostat and valemetostat in Japan.