Sex Differences in Disease Characteristics and Outcome in Adults with Acute Myeloid Leukemia from China

Background There is a male predominance of acute myeloid leukemia (AML) incidence, but data on disease characteristics and survival by sex are conflicting, and most from western countries. Nowadays, there are limited data from Asian countries on sex disparities in disease characteristics and outcome in AML.

Methods Data of consecutive newly-diagnosed elderly patients with AML at Peking University People's Hospital from January 2016 to June 2024 were reviewed. Clinical information, treatment regimens, cytogenetic and molecular data were obtained. Risk group classification was determined according to European LeukemiaNet (ELN) 2022 recommendation. Propensity score matching analysis was conducted in patients with favorable-, intermediate-, or adverse-risk to adjust for differences in baseline covariates (age, WBC, hemoglobin, platelet, blasts in bone marrow, albumin, bilirubin, estimated glomerular filtration rate [eGFR], lactate dehydrogenases [LDH], Charlson Comorbidity Index and Eastern Cooperative Oncology Group performance status) and therapy regimens (intensive vs. less intensive therapy) between male and female. Cumulative incidence of relapse (CIR) was estimated with Fine-Gray test, with non-relapse death being the competing risk. Relapse-free survival (RFS) and survival were estimated with the log-rank test. Cox regression model was used to identify variables associated with outcomes.

Results A total of 1811 patients was included in the study. 946 (52%) was male. Median age was 47 (IQR, 34-58) years. According to ELN risk classification, 685 (38%) patients was in favorable-risk; 461 (26%), intermediate-risk; and 665 (36%), adverse-risk. 1019 (56%) patients received intensive chemotherapy, 403 (22%) azacitidine plus venetoclax regimen; 389 (22%), low-dose cytarabine based chemotherapy. 527 (29%) patients received allo-transplant in the first CR. With a median follow-up of 15 (IQR, 6-29) months, 1182 (65%) patients achieved CR/CRi after first induction therapy; 1530 (85%), CR/CRi ultimately. 2-year CIR, 2-year RFS and 2-year survival rate were 35% (95%CI: 32%, 38%), 59% (56%, 62%) and 69% (67%, 72%), respectively.

At diagnosis, male patients had a higher hemoglobin (median value, 86 g/L vs. 83 g/L, P = 0.005), lower eGFR (99 mL/min vs. 105 mL/min, P < 0.001), higher LDH concentration (356U/L vs. 325U/L, P = 0.043) compared to female patients. Male patients had a higher rate of myelodysplasia-related cytogenetic abnormality (MRC) (22% vs. 17%, P = 0.008), myelodysplasia-related gene mutation (MRG) (30% vs. 23%, P = 0.001) and more number of gene mutations (2.6 ± 1.7 vs. 2.4 ± 1.6, P = 0.001). Including, ASXL1 (13% vs. 6%, P < 0.001), U2AF1 (8% vs. 3%, P < 0.001), SRSF2 (6% vs. 3%, P = 0.001), RUNX1 (11% vs. 7%, P = 0.002), CBL (4% vs. 2%, P = 0.008) and SETBP1 mutation (2% vs. 0.6%, P = 0.005) were more common in male; whereas NPM1 (16% vs. 21%, P = 0.011) and non-inframe bZIP CEBPA mutation (5% vs. 7%, P = 0.047) were more common in female. Moreover, male patients were more prevalent in ELN adverse-risk (39% vs. 34%, P = 0.027) and less prevalent in ELN intermediate-risk (24% vs. 28%, P = 0.054).

After performing PSM analysis, 269 pairs with favorable-risk, 186 pairs with intermediate-risk and 285 pairs with adverse-risk were included for comparison between male and female. In the favorable-risk cohort, male patients had lower CR/CRi rate after the first cycle (78% vs. 86%, P = 0.013), but comparable final CR/CRi rate (96% vs. 98%, P = 0.218). 2-year CIR (30% [23%, 36%] vs. 25% [18%, 31%], P = 0.033), 2-year probabilities of RFS (65% [58%, 72%] vs. 70% [63%, 77%], P = 0.036) and survival (81% [75%, 87%] vs. 86% [81%, 91%], P = 0.07) were inferior in the male patients. In the intermediate-risk cohort, no significantly difference in response rates and outcomes was observed between male and female patients. In the adverse-risk cohort, CR/CRi rates were comparable, whereas 2-year CIR (47% [39%, 56%] vs. 37% [29%, 44%], P = 0.080), 2-year probabilities of RFS (44% [36%, 52%] vs. 59% [51%, 67%], P = 0.007) and survival (55% [48%, 62%] vs. 62% [55%, 69%], P = 0.037) were inferior in the male patients.

Conclusions Male patients with AML from China were more likely to have adverse genetic characteristics and independently inferior outcome compared to the female patients. Sex-associated difference of relatively high proportion of MRC and MRG abnormalities might led to poor prognosis in male adults with AML.

No relevant conflicts of interest to declare.