Venetoclax Plus Conditioning Regimen for Patients With AML and FLT3-ITD-Mutated Undergoing AlloHSCT

Venetoclax plus a conditioning regimen, yielded high overall survival (OS) and low relapse rates among patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT) for high-risk acute myeloid leukemia (AML), according to findings from a study recently published in Annals of Medicine. 

Dr Xing-yu Cao, MD, Hebei Yanda Lu Daopei Hospital, Langfang, China, and coauthors aimed to evaluate the safety and efficacy of a conditioning regimen for alloHSCT containing venetoclax. They stated, “an optimal conditioning regimen that allows for a well-balanced antileukemia effect and limited toxicity is urgently needed.” 

The primary endpoint of this study was OS, and secondary endpoints included leukemia-free survival (LFS), relapse incidence (RI), non-relapse mortality (NRM), and safety of treatment. 

31 patients with a median age of 25 years and AML (with high-risk features like R/R leukemia or minimal residual disease positivity) who had undergone a median of 3 cycles of chemotherapy before transplantation were enrolled in this study. 

Next-generation sequencing was performed to observe the possibility of FLT3-ITD, NPM1, and CALR gene mutations in patients, which indicated that the FLT3-ITD gene mutation was present in 51.6% of patients. At the time of transplantation, 21 patients were in 1st complete remission, 4 were in 2nd complete remission, and 6 were in non-remission.

Patients were administered venetoclax at 400 mg daily, in combination with fludarabine at 30 mg/m2 daily, cytarabine at 2g/m2 daily, and G-CSF at 5μg/kg on days -14 and -10. Following this regimen, patients received a busulfan plus cyclophosphamide conditioning regimen (busulfan at 0.8mg/kg every 6 hours on days -9 to -6, and cyclophosphamide at 1g/m2 on days -5 to -4). 

Results indicated that the 600-day OS was 80.9% and the LFS was 81.3%, respectively. At the same time point, the RI was 6.9%, and the NRM was 11.7%. Cytopenia and infection were the most common grade 3 or higher treatment-related adverse events. The incidence of grade 3 to 4 acute graft-versus-host disease was 16.1%. 

As both primary and secondary endpoints were met, Dr Cao et al concluded that the results suggest “adding venetoclax to a MAC regimen of allo-HSCT was feasible, safe and effective for high-risk AML.

“More data and longer observation time are needed to further evaluate the efficacy of venetoclax as part of this regimen,” they added, “Studies to figure out which patients would benefit from this conditioning regimen are also needed, although this will be a challenging undertaking.” 

Source: 

Cao X, Chen J, Wang H, et al. Addition of venetoclax to myeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation in high-risk AML. Annals of Medicine. 2023;55(1):388-400. doi:https://doi.org/10.1080/07853890.2022.2164610