Outcomes with Lower-Intensity Therapy in TP53-Mutated AML

Most patients with acute myeloid leukemia (AML) and TP53 mutations have karyotypes that are associated with unfavorable risk. Recent data indicate that aggressive forms of AML marked by TP53 mutations appear more likely to respond to a 10-day regimen of decitabine, a relatively mild chemotherapy. In this study, researchers sought to understand whether the benefit is unique to decitabine or if other low-intensity therapies confer a similar benefit to this patient population.

Patients were tested for TP53 mutation using a whole-exome sequencing panel. After review of patients’ clinical and pathologic characteristics, outcomes were evaluated based on the presence of a TP53 mutation and by the type of treatment received. Of the 131 patients in the study cohort, 33 (25%) had TP53 mutation. Patients were treated with 1 of 4 different low-intensity options: 10-day decitabine (n = 34); 5-day decitabine or 7-day azacytidine (n = 39); cladribine plus low-dose cytarabine (n = 58).

The researchers found no significant difference in response rates or overall status by TP53 mutation status for any of the 4 treatment approaches. However, in patients with the TP53 mutation, there was a trend toward inferior response rates and overall survival (OS) among those who received either 5-day decitabine, 7-day azacytidine, or cladribine plus low-dose cytarabine. No inferior trend was seen in patients receiving 10-day decitabine. When comparing across groups, the combination of cladribine plus low-dose cytarabine was associated with the longest OS, and 10-day decitabine was associated with superior outcomes compared with 5-day decitabine in the cohort with TP53 mutation.

Although the results show a trend toward improved outcomes with some low-intensity regimens, further research is needed to assess the clinical significance of these preliminary findings.

Kadia TM, et al. ASCO Abstract 7017.

Related Items