Validation in Clinical Outcomes of Acute Myeloid Leukemia Patients Harboring RUNX1 Mutation: A Cohort Study and Meta-Analysis

Background: Acute myeloid leukemia (AML) with mutated RUNX1 (RUNX1^mut) was considered to have an unfavorable prognosis according to the 2017 European Leukemia Net risk stratification. However, recent studies reported that AML patients with RUNX1^mut have comparable survival outcomes to those with wild-type RUNX1 (RUNX1^wt).

Methods: This prospective cohort study was conducted between 2019 and 2021 on newly diagnosed Thai AML patients. Clinical outcomes comparing the patients with and without RUNX1 mutation was the major focus. In addition, a systematic review and meta-analysis were further performed to elucidate the outcomes of AML patients with RUNX1^mut. The Embase, MEDLINE, and Cochrane Central Register of Controlled Trials databases were independently searched by three investigators to identify relevant studies published from inception to April 1, 2022. These trials compared either complete remission (CR), overall survival (OS), relapse-free survival (RFS), or event-free survival (EFS) between AML with and without RUNX1^mut.

Results: In our cohort study, 135 patients (27: RUNX1^mut and 108: RUNX1^wt) were enrolled. There were significantly higher age and predominant proportion of secondary AML in the RUNX1^mut group (P=0.008 and 0.002, respectively). The median OS and RFS were not different between RUNX1^mut and RUNX1^wt groups, 9.1 vs. 12.2 months; P=0.268 and 9.1 vs. 10.5 months; P=0.488, respectively. Likewise, the survival outcomes remained similar between both groups when subgroup analysis on de novo AML patients with intermediate-risk cytogenetics. Subsequently, 21 eligible studies and our cohort study were included in a meta-analysis, representing 1,093 patients with RUNX1^mut and 6,929 patients with RUNX1^wt. The CR rate was significantly lower in the RUNX1^mut group, with a pooled odds ratio (OR) of 0.42. The OS, RFS, and EFS were also in favor of the RUNX1^wt group, with the pooled risk ratios (RRs) of 1.36, 1.36, and 1.37, respectively. Interestingly, a subgroup analysis of patients who had de novo AML with intermediate-risk cytogenetics demonstrated that the OS and RFS were nearly identical between both groups with pooled RRs of 1.28 (95%CI; 0.75-2.17; I²= 0%, P-value = 0.36) and 1.13 (95%CI; 0.62-2.04; I²= 63%, P-value = 0.70), respectively.

Conclusion: AML patients with RUNX1^mut seemed to confer poor prognosis due to a range of their concomitant unfavorable risks including secondary AML and elderly age group. Nonetheless, focusing on de novo AML with intermediate-risk cytogenetics, survival outcomes of AML patients harboring RUNX1^mut were comparable to RUNX1^wtones.

No relevant conflicts of interest to declare.