Session: 617. Acute Myeloid Leukemias: Commercially Available Therapies: Poster III
Hematology Disease Topics & Pathways:
AML, Acute Myeloid Malignancies, Diseases, Myeloid Malignancies
CEBPA mutation is a prevalent molecular abnormality in acute myeloid leukemia (AML). Recent studies have reported that in-frame mutations in bZIP domain of CEBPA(CEBPAbZIP-inf) delineate a unique subgroup of AML patients who exhibit favorable prognosis to conventional chemotherapeutic regimens. Furthermore, CEBPA mutations are implicated in activating the BCL2 P2 promoter, a process facilitated by their interaction with nuclear factor-κB (NF-κB) p50, thereby enhancing BCL2 expression in hematopoietic cell lines. Nevertheless, the specific impact of BCL2 inhibitor venetoclax on CEBPAbZIP-inf AML patients remains understudied. Therefore, this study retrospectively analyzed the clinical characteristics, co-mutational spectrum, and the impact of induction regimens on the prognosis of patients with acute myeloid leukemia (AML) harboring CEBPAbZIP-inf.
Method:
A total of 103 de novo CEBPAbZIP-inf AML patients with biological data were enrolled, 44 cases were inducted by conventional “7+3” intensive chemotherapy (IC), 20 cases were by venetoclax plus hypomethylating agent regimens (VEN+HMA) and 27 cases were by venetoclax plus intensive chemotherapy (VEN+IC). Clinical characteristics, co-mutational spectrum, overall response rate, composite complete response (CRc) rate, overall survival (OS), and event free survival (EFS) were analyzed.
Results:
The age of patients in the VEN+HMA group is greater than that of the IC and VEN+IC groups. The median age was 47.0 (IC), 69.0 (VEN+HMA) and 42.0 (VEN+IC) years at diagnosis respectively. Co-mutation of ASXL1/2(20%), TET2(40%) and NPM1(20%) are relatively more common among the VEN+HMA cohort (p=0.0051, p=0.02, p=0.0051, respectively).
35(79.55%) patients attained CR/CRi after once cycle of induction therapy, and 11(31.4%) patients relapsed in IC group; 16(80%) patients attained CR/CRi, 8(50%) relapsed in VEN+HMA group; simultaneously, 26(96.3) patients attained CR/CRi, 9(34.6%) relapsed in VEN+IC group. The median follow-up of the patients in IC, VEN+HMA and VEN+IC was 815.0days, 599.0days and 673.0days, respectively. The median OS was not reached, 652.0days and not reached. In patients treated with IC and VEN+IC, the median OS was significantly longer compared with that in the VEN+HMA group (IC vs.VEN+HMA, p= 0.0025; VEN+IC vs. VEN+HMA, p=0.0183), but no significant difference was observed when comparing IC and VEN+IC group (IC vs. VEN+IC p= 0.928). The median EFS was not reached, 439.0days and not reached (IC vs.VEN+HMA, p= 0.168; VEN+IC vs. VEN+HMA, p= 0.227; IC vs. VEN+IC p= 0.915). When the patients were analyzed by age stratification, regardless of whether the patients are aged 60 or younger, or older than 60, there is no significant difference in OS and EFS among the three cohorts. The median OS of the patients in the IC, VEN+HMA and VEN+IC was not reached, not reached and not reached (IC vs.VEN+HMA, p= 0.746; VEN+IC vs. VEN+HMA, p= 0.657; IC vs. VEN+IC p= 0.704), and the EFS was not reached, 222.0days and not reached in patients aged 60 or younger (IC vs.VEN+HMA, p= 0.0904; VEN+IC vs. VEN+HMA, p= 0.204; IC vs. VEN+IC p=0.713). The median OS of the patients in the IC, VEN+HMA and VEN+IC was not reached, 652 and not reached (IC vs.VEN+HMA, p= 0.522; VEN+IC vs. VEN+HMA, p= 0.497; IC vs. VEN+IC p= 0.617), and the EFS was 294.0days, 790.0days and not reached in patients older than 60 (IC vs.VEN+HMA, p= 0.267; VEN+IC vs. VEN+HMA, p= 0.431; IC vs. VEN+IC p=0.299).
Conclusion:
In conclusion, IC, VEN + HMA, VEN+IC regimens showed similar CRc rates after one cycle of induction therapy, and had no significant impact on the prognosis of CEBPAbZIP-inf patients.
Disclosures: No relevant conflicts of interest to declare.
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