BEAT Chemofree Regimen for Relapsed/Refractory and De Novo T-ALL

Background: Relapsed or refractory (R/R) and unfit T-cell acute lymphoblastic leukemia (T-ALL) have limited therapeutic options and a poor prognosis, with a 5-year overall survival rate of 20% and a complete response (CR) rate around 36%. Our previous study found that tucidinostat plus pediatric-inspired chemotherapy improves the survival of T-ALL. Venetoclax demonstrated high sensitivity in vitro and in vivo for T-ALL, particularly early T-cell precursor lymphoblastic leukemia (ETP-ALL), and exhibited synergistic therapeutic effects with l-asparaginase and dexamethasone. Therefore, we hypothesized that the BEAT chemofree regimen (Bcl-2 inhibitor, dExamethasone, Aaspargase, and Tucidinostat) would be safe and effective for R/R and de novo T-ALL.

Methods: BEAT chemofree regimen consists of bcl-2 inhibitor, dexamethasone, aspargase, and tucidinostat. Patients with R/R and de novo T-ALL were enrolled in this study and received BEAT chemofree regimen including venetoclax (100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-14), tucidinostat and dexamethasone (10 mg on days 1-14) and pegaspargase (2000IU on day 3). This is a pilot study and we intend to conduct a multicenter randomized controlled trial in order to investigate and validate the efficacy and safety of the chemofree regimen in T-ALL.

Results: From January 2023 to June 2024, 6 patients with R/R T-ALL and 6 patients with de novo T-ALL were enrolled. For R/R T-ALL, the median age was 26 years (range 19-34 years), 67% were male, 100% were Asian, 4 had a diagnosis of ETP-ALL and 2 of Non ETP-ALL, 6 (100%) had received more than two lines of chemotherapy and 1 had received CD7 CAR-T therapy. For de novo T-ALL, the median age was 53 years (range 18-62 years), 73% were male, 100% were Asian, 4 had a diagnosis of ETP-ALL and 2 of Non ETP-ALL. Among the R/R T-ALL patients, 3 (50%) patients CR or CR with incomplete count recovery (CRi), including 2 (33%) patients achieved MRD <10^-4. One (17%) patient achieved partial remission (PR). The overall response rate (ORR) for R/R T-ALL is 67%. Among the de novo patients, 6 (100%) achieved CR/CRi including 4 (67%) achieved MRD<10^-4. The ORR for de novo T-ALL is 100%. The safety profile of BEAT regimen is well-tolerated in both R/R and de novo T-ALL. The most common grade 3-4 adverse events (AEs) of R/R T-ALL were neutropenia (67%), anemia (67%), thrombocytopenia (67%), febrile neutropenia (33%), lung infection (17%), septicemia (17%) and hypocalcemia (33%). The most common grade 3-4 AEs of de novo T-ALL were neutropenia (83%), anemia (67%), thrombocytopenia (34%), febrile neutropenia (17%), lung infection (17%) and ALT increased (17%). There were no gastrointestinal disorders of grade 3-4 or serious AEs of grade 5.

Conclusion: BEAT chemofree regimen is a promising and well-tolerated regimen in R/R and de novo T-ALL, with high CRc and ORR.

No relevant conflicts of interest to declare.

Venetoclax (100 mg on day 1, 200 mg on day 2, and 400 mg on days 3 to 14), Tucidinostat (10 mg on days to14) was administered for relapsed/refractory and de novo T-ALL.