OBJECTIVES: To evaluate the effect of ethnicity on the efficacy of FLT3 inhibitors (FLT3i) for relapsed or refractory acute myeloid leukemia (R/R AML).

METHODS: This is a systematic review with direct meta-analysis. Structured searches were conducted on Medline, Lilacs, and Embase. Additionally, a complementary search was conducted. Studies that compared a FLT3i with salvage therapy for the treatment of R/R AML in patients with FLT3 mutation were selected. The meta-analysis was conducted through the inverse variance method and the random-effects models were calculated by the DerSimonian and Laird method. Hazard ratios (HR) and relative risks (RR) were reported with their 95% confidence interval (95%CI).

RESULTS: Three studies were included. ADMIRAL and COMMODORE evaluated giltiritinib and QuANTUM evaluated quizartinib compared to salvage therapy. The data from ADMIRAL was quite complete regarding ethnicity, but QuANTUM did not report the HRs and 95%CIs for the Black or the “other” categories. COMMODORE only included Asian patients. The magnitude of effect of the FLT3i compared to salvage therapy seems higher in the Asian subgroup compared to the other ethnic groups (HR=0.55, 95%CI=0.32-0.94 vs. HR=0.74, 95%CI=0.60-0.90). This result was driven by the effect of gilteritinib, though. There was no indication that it would be true for quizartinib as well. Further studies are necessary to evaluate this hypothesis since no difference between subgroups was observed in the random-effects model (p-value=0.32). The fixed-effects model, though, showed a p-value=0.05. There was basically no difference in magnitude of effect in the white population between ADMIRAL and QuANTUM (HR=0.72, 95%CI=0.0.52-1.00 and HR=0.75, 95%CI=0.57-1.01).

CONCLUSIONS: It is unclear whether ethnicity is an effect modifier between FLT3i and salvage therapy because of relatively small samples and the loss of randomization derived from the subgroup analysis. Nevertheless, this matter surely deserves further investigation.