Objective: T-cell acute lymphoblastic leukemia (T-ALL) is a type of leukemia with poor prognosis and high relapse rate, lacking effective targeted therapies. Therefore, it is urgent to find new targeted therapy strategies. This study aims to investigate the efficacy and safety of first-line treatment regimen containing chidamide in the therapy of T-ALL, providing clinical evidence for chidamide as a new therapeutic option for patients with T-ALL.

Methods: We conducted a retrospective analysis of 10 patients with T-ALL treated at the Second Hospital of Hebei Medical between February 2020 and July 2024. All the patients underwent the Chidamide (15-30 mg/dose, twice weekly) combination with chemotherapy in induction and maintenance therapy. We retrospectively studied the effectiveness and safety of this regimen.

Results: Among the 10 T-ALL patients, 6 were male (60%), with a median age of 39 years (range 25-75). According to the EGIL classification criteria, the cases were classified as follows: 5 cases of ETP-ALL (50%), 1 case of Pre T-ALL (10%), and 4 cases of cortical T-ALL (40%). Next-generation sequencing for 9 patients demonstrated that 8 patients had gene mutations (median, three mutations per patient). The most frequently mutated genes were NOTCH1 (44.4%), WT1 (44.4%), PHF6 (22.2%), IDH2 (22.2%), FLT3 (11.1%) and JAK3 (11.1%). The induction and maintenance chemotherapy regimens included traditional VCDP/VCMP/VCLP protocols. Patients received chidamide combined with induction chemotherapy during the initial induction phase, continuing with chidamide plus chemotherapy for maintenance after achieving remission. After induction remission therapy, all patients achieved complete remission, with a CR rate of 100%. 2 of these patients underwent hematopoietic stem cell transplantation (HSCT) after chidamide treatment and have remained in stable remission. As of July 2024, the median follow-up time was 18.4 months (range 8.6-48.5). 6 patients were alive, and 4 had died. The median progression-free survival (PFS) and overall survival (OS) were not reached. The 1-year and 2-year PFS rates were 80% and 66.7%, respectively, while the 1-year and 2-year OS rates were 78.8% and 56.3%, respectively. Among the 8 patients who did not receive transplantation, 7 patients had at least one minimal residual disease (MRD) result, with the best MRD-negative rate being 100% (7/7). Five patients maintained MRD negativity, one patient converted from MRD-positive to MRD-negative, and one patient experienced an extramedullary relapse with MRD converting from negative to positive after the 4th cycle. Analysis of PFS and OS among different EGIL subtypes of T-ALL showed no statistically significant differences (P > 0.05). Treatment-related adverse events were primarily bone marrow suppression, with an incidence of ≥ Grade III hematological toxicity at 75%. Infections and gastrointestinal reactions were the most common non-hematological adverse reactions, which were tolerable, with no treatment-related deaths.

Conclusion: Chidamide, a novel histone deacetylase (HDAC) subtype-selective inhibitor, has made significant progress in the treatment of T-cell lymphoma. Additionally, it has also played a role in salvage therapy for relapsed and refractory acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). We found that Chidamide combined with standard chemotherapy is a safe and effective as the first-line treatment in T-ALL significantly reducing disease relapse and allowing long-term disease-free survival even in non-transplant patients. Our research provides a foundation for using Chidamide as a first-line treatment for T-ALL.

Disclosures

No relevant conflicts of interest to declare.

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2024
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