Treatment of adult TP53-mutated acute myeloid leukemia (AML) with venetoclax plus a hypomethylating agent (HMA) may result in improved efficacy, according to results from a retrospective study published in the British Journal of Haematology.
The presence of mutated TP53 in patients with AML confers an exceptionally poor prognosis. Additionally, mutated TP53 is more common in older patients with inferior fitness, in patients with therapy-related AML, and in patients with AML with complex cytogenetics. Efficacy of standard induction therapy in TP53-mutated AML is typically low and brief.
Researchers retrospectively evaluated clinical outcomes in 31 adult patients with TP53-mutated AML treated with venetoclax plus an HMA at City of Hope National Medical Center in Duarte, California, between June 2016 and April 2019.
Continue Reading
Sixteen patients (52%) experienced a response to treatment, with 7 complete responses and 9 complete responses with incomplete count recovery. Responses occurred after a median of 2 cycles of treatment (range, 1-3).
This study defined measurable residual disease (MRD) as greater than 0.01% by multiparameter flow cytometry in a reference laboratory and evaluated MRD in 10 of the responders. Of these 10 patients, 7 achieved MRD negativity.
Prior treatment with single-agent HMA was associated with a 14% response rate compared with a 63% response rate in HMA-naive patients (P =.025). Response rate was similar across sex, type of AML, presence of additional mutations, type and length of HMA therapy, age, cytogenetics, and receipt of prior allogeneic hematopoietic stem cell transplantation (alloHCT).
In responders, the median leukemia-free survival was 234 days (95% CI, 101-329), and the median overall survival was 329 days (95% CI, 284-not reached). Five responders (31%) underwent alloHCT in CR.
The authors noted that although these preliminary results appeared better than the “dismal outcomes reported in patients with TP53-mutated AML when treated with conventional combination chemotherapy,” frequent relapses and relatively short leukemia-free survival indicate a need for further improvements, potentially with venetoclax in combination with HMAs serving as a therapeutic backbone. This potential backbone could also help bridge more of these patients to alloHCT.
Reference
1. Aldoss I, Zhang J, Pillai R, et al. Venetoclax and hypomethylating agents in TP53-mutated acute myeloid leukaemia [published online August 22, 2019]. Br J Haematol. doi:10.1111/bjh.16166
