KEY TAKEAWAYS
- The study aimed to investigate the predictive value of WT1 mRNA dynamics in VEN combination therapy outcomes for AML patients.
- Researchers noticed that WT1 mRNA dynamics serve as a valuable indicator for evaluating the long-term prognosis of VEN combination therapy in AML patients.
Wilms’ tumor gene 1 (WT1) mRNA quantification is a useful marker of measurable residual disease in acute myeloid leukemia (AML). However, whether monitoring the WT1 mRNA levels may predict the outcome of venetoclax (VEN) combination therapy in AML is not reported.
Honami Sato and the team aimed to elucidate whether WT1 mRNA dynamics could predict long-term prognosis.
Researchers performed an inclusive analysis of 33 patients with untreated or relapsed/refractory (R/R) AML undergoing VEN combination therapy. Peripheral blood samples were collected and evaluated for WT1 dynamics throughout treatment.
The median age was 73 years (range 39-87), with azacitidine combined with VEN in 91% of patients. Overall, the median overall survival (OS) was 334 days (95% CI 210-482), with a complete remission (CR) plus CR with incomplete hematologic recovery rate of 59%. A 1-log reduction of WT1 mRNA values by the end of cycle 2 of treatment correlated significantly with better OS and event-free survival (EFS) (median OS 482 days vs. 237 days, P = 0.049; median EFS 270 days vs. 125 days, P = 0.02).
Post-treatment negativity of WT1 mRNA values was also associated with significantly improved OS and EFS (median OS 482 days vs. 256 days, P = 0.02; median EFS not reached vs. 150 days, P = 0.005). Multivariate analysis confirmed these parameters as strong EFS predictors (HR 0.26, P = 0.024 and HR 0.15, P = 0.013, respectively). Additionally, an increase in WT1 mRNA values was correlated with relapse.
The study concluded that WT1 mRNA dynamics serve as a valuable marker for assessing the long-term prognosis of VEN combination therapy for AML.
The study received open-access funding from Akita University, Otsuka Pharmaceutical, NOVARTIS Foundation (Japan) for the Promotion of Science, Pfizer Japan, Astellas Pharma, Ono Medical Research Foundation and Asahikasei.
Source: https://pubmed.ncbi.nlm.nih.gov/38334897/
Sato H, Kobayashi T, Kameoka Y, et al. (2024). “Prognostic impact of peripheral blood WT1 mRNA dynamics in patients with acute myeloid leukemia treated with venetoclax combination therapy.” Int J Clin Oncol. 2024 Apr;29(4):481-492. doi: 10.1007/s10147-024-02480-9. Epub 2024 Feb 9. PMID: 38334897; PMCID: PMC10963556.
