No abstract

In recent years, one of the most promising advances in the treatment of acute myeloid leukemia (AML) is the combination of a hypomethylating agent (HMA) with the BCL2 inhibitor venetoclax (VEN). To better understand the key factors associated with the response of VEN plus HMA, 212 consecutive AML patients were retrospectively recruited to establish and validate a scoring system for predicting the primary resistance to VEN‐based induced therapy. All AML patients were divided randomly into a training set (n = 155) and a validation set (n = 57). Factors were selected using a multivariate logistic regression model, including FAB‐M5, myelodysplastic syndrome‐secondary acute myeloid leukemia (MDS‐sAML), RUNX1‐RUNX1T1 and FLT3‐ITD mutation (FLT3‐ITDm). A nomogram was then constructed including all these four predictors. The nomogram both presented a good performance of discrimination and calibration, with a C‐index of 0.770 and 0.733 in the training and validation set. Decision curve analysis also indicated that the nomogram was feasible to make beneficial decisions. Eventually a total scoring system of 8 points was developed, which was divided into three risk groups: low‐risk (score 0–2), medium‐risk (score 3–4), and high‐risk (score 5–8). There was a significant difference in the nonremission (NR) rate of these three risk groups (22.8% vs. 60.0% vs. 77.8%, p < 0.001). After adjustment of the other variables, patients in medium‐ or high‐risk groups also presented a worse event‐free survival (EFS) than that in the low‐risk group (hazard ratio [HR] = 1.62, p = 0.03). In conclusion, we highlighted the response determinants of AML patients receiving a combination therapy of VEN plus HMAs. The scoring system can be used to predict the resistance of VEN, providing better guidance for clinical treatment.

No abstract