Clinical Outcomes of Tucidinostat Therapy for Relapsed/Refractory Adult T-Cell Leukemia-Lymphoma (ATL) in Clinical Practice

Abstract

【Objective】 Tucidinostat, approved for relapsed/refractory adult T-cell leukemia-lymphoma (ATL) treatment in June 2021 in Japan, demonstrated an objective response rate (ORR) of 30.4%, progression-free survival (PFS) of 1.7 months (95% CI: 0.8-7.4), and overall survival (OS) of 7.9 months (95% CI: 2.3-18.0) in a phase IIb trial for 23 cases of relapsed/refractory adult T-cell leukemia-lymphoma (ATL) in Japan. We report the treatment results of this agent in Miyazaki Prefecture. 【Methods】 We retrospectively analyzed the treatment results of relapsed/refractory ATL patients who received Tucidinostat at 6 facilities within the Miyazaki prefecture, and HTLV-1 endemic area in southwest Japan, after its approval. All clinical procedures for patients were part of routine care, and the requirement for written patient consent was waived by the committee in view of the retrospective nature of this study. Approved study protocols were presented on the web site in an opt-out format, ensuring patients had the right to refuse participation in the study. In accordance with these protocols, clinical information was then collected. 【Results】 From October 2021 to July 2023, Tucidinostat was administered to 24 cases of relapsed/refractory ATL. The median age at the start of administration was 72.5 (41-85), with 13 cases of the acute type, 7 cases of the lymphoma type, and 4 cases of poor-prognosis chronic type. The median number of prior treatment regimens was 2 (1-4), with 19 cases of multi-drug combination chemotherapy, 18 cases of mogamulizumab, and 5 cases of oral chemotherapy. There were no cases of transplantation. The period from prior treatment to Tucidinostat administration was 3.2 months (0-27.5 months), and the disease stage at the start of Tucidinostat administration was relapse in 7 cases and refractory in 17 cases. The starting dose was 40mg/day (twice a week) in 19 cases and 20mg/day (twice a week) in 4 cases, with a median number of total treatment courses of 3 (1-20). Of the 24 cases,19 had their dose reduced or treatment suspended because of myelosuppression. The best treatment response was complete response(CR) in 5 cases, parcial response (PR) in 8 cases, Stable Disease(SD) in 8 cases, with an efficacy rate (CR/PR) of 54.2%. The PFS after the start of treatment was 3.7 months (1.8-7.8), and the OS after the start of treatment was 8.6 months. The reason for discontinuation of administration were progression disease in 15 cases, intolerance in 1 case (skin rash in 1 case), and severe complications in 1 case (cryptococcal meningitis). In the Cox proportional hazards model analysis, considering the clinical characteristics at the initiation of Tucidinostat, the initial sIL-2R level negatively impacted PFS. PFS was then stratified using an sIL-2R cutoff of 5000 U/mL, showing a Median Survival Time (MST) of PFS: 0.65 months for those below the cutoff versus 0.15 months for those above it, p=0.006 (log-rank).“A similar trend was observed for OS (Median OS: not reached vs. 0.53 months, p=0.032 (log-rank)). 【Conclusion】 In relapsed/refractory ATL, Tucidinostat achieved treatment results similar to those in the phase IIb trial in clinical practice. In particular, for cases with an sIL2-R value of less than 5000, it was suggested that Tucidinostat may be a meaningful treatment option.