The Outcome of Older Patients with Acute Myeloid Leukemia Based on the SEER Database in the Era of Targeted Therapy

doi:10.21203/rs.3.rs-8127508/v1

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The Outcome of Older Patients with Acute Myeloid Leukemia Based on the SEER Database in the Era of Targeted Therapy

https://doi.org/10.21203/rs.3.rs-8127508/v1

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Large-scale real-world studies are essential to assess the outcome of older acute myeloid leukemia (AML) patients in the targeted therapy era. Using the Surveillance, Epidemiology, and End Results (SEER) database, we investigated the epidemiology, clinical characteristics, and survival outcome of AML patients aged ≥ 60 years. From 2000 to 2021, the incidence of older AML patients showed an upward trend, with an Annual percentage change (APC) of 0.80% (95% CI: 0.35–1.27, P = 0.0015). Unexpectedly, the proportion of therapy-related myeloid neoplasm (t-MN) decreased with age (60–69 years, 5.7%; 70–79 years, 3.9%; 80–89 years, 1.8%; ≥90 years, 1.0%; P < 0.001). Among older AML patients, the 1-year overall survival (OS) rate increased from 19.6% in 2000–2008, to 24.8% in 2009–2016, and further to 29.6% in 2017–2021 (P<0.001). Correspondingly, the 5-year OS rate rose from 5.0 % to 7.1 % and finally to 9.7 % (P<0.001). Age-stratified analysis demonstrated that among patients aged 60–69, the 1-year OS rate reached 43.0% in 2017–2021 (P < 0.0001), with 3-year and 5-year OS rates increasing to 24.4% and 20.3%, respectively (P < 0.0001). Similarly, in the 70–79 years group, the 1-year, 3-year, and 5-year OS rates improved to 30.1%, 11.1%, and 7.07% during 2017–2021(P < 0.0001). For those aged 80–89, the 1-year OS rate rose from 8.85% to 12.2% to 15.5%, while among the very elderly (≥ 90 years), it reached 7.97% in 2017–2021(P<0.05). These findings confirm that targeted therapies have substantially improved survival across all older AML patient groups, including the super-elderly (≥ 90 years).

Acute myeloid leukemia

older patients

survival

targeted therapy

SEER database

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by a block in myeloid differentiation and aberrant proliferation of immature myeloid progenitors [1]. It is the most common type of acute leukemia among adults [2–3]. The median age at diagnosis is 68–70 years, and the incidence increases with advancing age, with over 60% of AML cases diagnosed at ≥ 60 years of age [4]. Thus, older patients make up the majority of all patients with AML.

Although there is currently no unified standard for the definition and age threshold of older AML patients, most guidelines and clinical trials generally recognize age ≥ 60 years as older AML[5–7]. Because of comorbidities, compromised organ function, and poor performance status, a substantial proportion of older AML patients are ineligible for intensive chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) [8–9]. Additionally, older patients with AML exhibit a higher frequency of adverse-risk genetic features [7, 10–12]. As a result, the prognosis for older AML patients is extremely poor, with a median overall survival (OS) of only 4 months [7, 13]. The 5-year OS rate is below 25% for AML patients aged 60–65 years, drops to less than 10% for those aged 70 years and older, while it approaches 50% for patients under 60 years [7]. This demonstrates a continuous decline in survival with advancing age. As the global population ages, the management of older AML patients faces numerous challenges.

Low-intensity regimens, including hypomethylating agents (HMAs) such as azacitidine, decitabine, or low-dose cytarabine (LDCA), are the preferred option for older AML patients who are unsuitable for intensive chemotherapy. However, the efficacy of HMA monotherapy is limited, with overall response rates between 10% and 50%, a median time to best response of 3.5–4.3 months, and a median OS of only 7.7–10.4 months[14–16]. LDCA yields even poorer outcomes, with complete remission (CR) plus CR with incomplete blood count recovery (CRi) rates of 11%-19%, and a median OS of less than 6 months[16–18]. These results highlight the urgent need for effective and well-tolerated treatment options for older AML patients. As the molecular pathogenesis of AML has gradually been elucidated, several novel targeted therapies have been approved by the Food and Drug Administration (FDA) for the treatment of AML since 2017. These include inhibitors targeting FMS-like tyrosine kinase 3 (FLT3), isocitrate dehydrogenase(IDH)1, IDH2, B-cell lymphoma 2 (BCL-2), and so on[3, 19–21]. Targeted therapies have significantly improved the remission rates and survival in older AML patients[19–21]. In particular, the combination of venetoclax with HMA therapy has become the first-line treatment for those ineligible for intensive chemotherapy[22–24].

The treatment of older AML parients has shifted toward personalized and precision therapy guided by genetic profiling. However, it still requires validation whether the prognosis for older AML patients has improved in the era of targeted therapies in real-world settings. As a result, this study utilizes the Surveillance, Epidemiology, and End Results (SEER) database to assess the outcomes of older AML patients over the past 20 years.

Data source and patient selection

Data were extracted from the SEER 17-registry database (2000–2021) using SEER*Stat software (version 8.4.3). Patients diagnosed with AML, according to the International Classification of Diseases for Oncology, Third Edition (ICD-O-3) codes 9840/3, 9861/3, 9865/3, 9867/3, 9869/3, 9870/3, 9871/3, 9872/3, 9873/3, 9874/3, 9891/3, 9895/3, 9896/3, 9897/3, 9910/3, 9911/3, 9920/3, and 9931/3 from 2000 to 2019, were included in this study. Exclusion criteria were: (1) diagnosis of acute promyelocytic leukemia (ICD-O-3 code 9866/3); (2) lack of confirmation through histological, immunophenotypic, and/or genetic studies; (3) undocumented survival times. The flow diagram of patient selection is shown in Fig. 1. Clinical information included age at diagnosis, sex, race, year of diagnosis, marital status, radiation therapy, chemotherapy, first malignant primary indicator, vital status, cause of death, and survival months. Patients were stratified by age into younger (<60 years) and older (≥ 60 years) AML. A total of 69,581 patients were enrolled, including 47,384 older AML patients and 22,197 younger patients. Given that azacitidine, a type of HMAs, was approved in December 2008 for treating older AML patients, and considering the subsequent approval of multiple novel targeted therapies for AML starting in 2017, we divided the year of diagnosis into 2000–2008, 2009–2016, and 2017–2021, representing the eras of LDAC, HMAs therapy, and targeted therapy, respectively.

Statistical analysis

Incidence rates were calculated per 100,000 person-years and age-adjusted to the 2000 US Standard Population by SEER*Stat. Annual percentage change (APC) was calculated using the weighted least-squares method. To compare baseline characteristics, the Wilcoxon test was used for two-group comparisons and the Kruskal-Wallis test with Dunn’s post hoc test for multi-group comparisons. Categorical variables were compared using the chi-square test. OS was defined as the time from AML diagnosis to death from any causes. Survival analyses utilized the reverse Kaplan-Meier method to estimate the median follow-up time, differences in survival curves between groups were compared using the log-rank test. To evaluate the number and percentage of cause of death at 3-month periods, histograms and stacked proportional histograms were assessed between 2000 and 2021 overall and by every 5-year period.

All statistical analyses were performed by R software (version 4.2.1) and SPSS version 25.0. Tests were two-sided, and p value less than 0.05 was considered statistically significant.

Incidence of older AML patients

From 2000 to 2021, the incidence of AML in patients under 60 years remained stable, with an APC of -0.14% (95% confidence interval [CI]: -0.47 to -0.19, P = 0.3941). In contrast, a significant increasing trend was observed among patients aged ≥ 60 years, with an APC of 0.80% (95% CI: 0.35–1.27; P = 0.0015). The annual age-adjusted incidence rate of AML ranged from 3.45 to 4.20 per 100,000 (Fig. 2A). Males exhibited a higher incidence than females (4.27–5.18 vs. 2.82–3.50 per 100,000) (Fig. 2B). The incidence rate increased markedly with age. Among patients under 60 years, the annual age-adjusted incidence was 1.29–1.54 per 100,000, whereas it rose sharply to 13.86–17.82 per 100,000 in those aged ≥ 60 years. Stratified by age groups, the incidence rate was 8.25–9.51 per 100,000 for patients aged 60–69 years, 16.36–21.17 per 100,000 for those aged 70–79 years, and 21.82–30.24 per 100,000 for those aged ≥ 80 years (Fig. 2C).

Clinical characteristics of older AML patients

A total of 69,581 patients were included, among whom 47,384 (68.1%) were older AML patients (Table 1). The median age of older group was 75 years, with 30.6% age 60–69, 38.2% age 70–79, 26.7% age 80–89, and 4.5% 90 years and over. The older AML patients cohort was predominantly male (56.3%) and white (85.1%). Compared to patients aged < 60 years, older AML patients were significantly less likely to receive radiotherapy or chemotherapy, and this trend declined progressively with advancing age (Tables 1 and 2). Notably, older patients had a significantly higher proportion of non-AML as their first primary malignancy than those younger counterparts (37.3% vs 16.5%, P < 0.001) (Table 1). According to the 2016 World Health Organization (WHO) classification, AML with myelodysplasia-related changes (AML-MRC) was more frequent in older patients (11.1%) than in those < 60 years (5.3%), peaking in the 70–79 year group (12.2%) (Tables 1 and 2). Interestingly, no significant difference was observed in the incidence of therapy-related myeloid neoplasm (t-MN) between patients aged ≥ 60 years (3.7%) and those < 60 years (3.8%) (Table 1). However, when stratified by age, the incidence of t-MN showed a declining trend with increasing age (60–69 years, 5.7%; 70–79 years, 3.9%; 80–89 years, 1.8%; ≥90 years, 1.0%; P < 0.001) (Table 2). Additionally, core-binding factor (CBF) AML was significantly less common in the older group (1.7% vs. 6.3% in patients < 60 years; P = 0.028) (Table 1).

Table 1
Clinical characteristics of AML patients.
Characteristic	ALL patients (n = 69581)	<60 years (n = 22197)	≥ 60 years (n = 47384)	P-value
Median age (years) (IQR)	68 (55–78)	45 (29–54)	75 (68–81)	<0.001
Sex, n (%)				<0.001
Male	38278 (55.0)	11623 (52.4)	26655 (56.3)
Female	31303 (45.0)	10574 (47.6)	20729 (43.7)
Race, n (%)				<0.001
White	57307 (82.4)	16974 (76.5)	40333 (85.1)
Black	5811 (8.4)	2553 (11.5)	3258 (6.9)
Other	6220 (8.9)	2543 (11.4)	3677 (7.8)
Unknown	243 (0.3)	127 (0.6)	116 (0.2)
WHO classification(2016), n(%)				0.028
CBF	2225 (3.2)	1400 (6.3)	825(1.7)
Other genetic abnormalities	900 (1.3)	477 (2.2)	423(0.9)
NOS	57416 (82.5)	18298 (82.4)	39118(82.6)
t-MN	2623 (3.8)	853 (3.8)	1770(3.7)
AML-MRC	6417 (9.2)	1169 (5.3)	5248(11.1)
Radiation, n (%)				<0.001
Yes	3063 (4.4)	2196 (9.9)	867(1.8)
None/Unknown	66518 (95.6)	20001 (90.1)	46517(98.2)
Chemotherapy, n (%)				<0.001
Yes	48424 (69.6)	19896 (89.6)	28528(60.2)
No/Unknown	21157 (30.4)	2301 (10.4)	18856(39.8)
First malignancy, n (%)				<0.001
Yes	48262 (69.4)	18543 (83.5)	29719(62.7)
No	21319 (30.6)	3654 (16.5)	17665(37.3)
Abbreviations: IQR, interquartile range; CBF, core binding factor; t-MN, therapy-related myeloid neoplasm; AML-MRC, AML with myelodysplasia-related changes.

Table 2
Clinical characteristics of older AML patients among different age groups.
Characteristic	60–69 years (n = 14522)	70–79 years (n = 18123)	80–89 years(n = 12632)	≥ 90 years(n = 2107)	P-value
Sex, n (%)					<0.001
Male	8306 (57.2)	10565 (58.3)	6846 (54.2)	938 (44.5)
Female	6216 (42.8)	7558 (41.7)	5786 (45.8)	1169 (55.5)
Race, n (%)					<0.001
White	12101 (83.3)	15411 (85.0)	10983 (87.0)	1838 (87.3)
Black	1221 (8.4)	1218 (6.7)	703 (5.6)	116 (5.5)
Other	1170 (8.1)	1446 (8.0)	915 (7.2)	146 (6.9)
Unknown	30 (0.2)	48 (0.3)	31 (0.2)	7 (0.3)
WHO classification(2016), n(%)					<0.001
CBF	380 (2.6)	276 (1.5)	150 (1.2)	19 (0.9)
Other genetic abnormalities	145 (1.0)	157 (0.9)	110 (0.9)	11 (0.5)
NOS	11623 (80.0)	14780 (81.6)	10827 (85.7)	1888 (89.6)
t-MN	820 (5.7)	698 (3.9)	232(1.8)	20 (1.0)
AML-MRC	1554 (10.7)	2212 (12.2)	1313 (10.4)	169 (8.0)
Radiation, n (%)					<0.001
Yes	605 (4.2)	220 (1.2)	39 (0.3)	3 (0.1)
None/Unknown	13917 (95.8)	17903 (98.8)	1259 (99.7)	2104 (99.9)
Chemotherapy, n (%)
Yes	11610 (79.9)	11551 (63.7)	4940 (39.1)	427 (20.3)
No/Unknown	2912 (20.1)	6572 (36.3)	7692 (60.9 )	1680 (79.7)
First malignancy, n (%)					<0.001
Yes	9595 (66.1)	10964 (60.5)	7773 (61.5)	1387 (65.8)
No	4927 (33.9)	7159 (39.5)	4859 (38.5)	720 (34.2)
Abbreviations: CBF, core binding factor; t-MN, therapy-related myeloid neoplasm; AML-MRC, AML with myelodysplasia-related changes.

The overall outcome of older AML patients

The median follow-up time was 101 months (range, 1-263 months; 95% CI, 99–103 months) for the entire cohort. Among older AML patients, median OS was only 3 months, with a 5-year OS rate of 6.91% (95% CI: 6.66–7.17%). In contrast, patients younger than 60 years exhibited a significantly longer median OS of 22 months and a higher 5-year OS rate of 39.2% (95% CI, 38.6–39.9%), highlighting a stark disparity in survival outcomes between older and younger patients (P < 0.001) (Fig. 3A).

Further age-stratified analysis showed a progressive decline in survival with increasing age among older AML patients. The median OS was 8 months in patients aged 60–69 years, decreased to 3 months in those aged 70–79 years, and dropped to only 1 month in the 80–89 years age group. Notably, patients aged 90 years or older had an extremely poor prognosis, with a median OS of 0 months. A corresponding reduction was also observed in long-term survival rates. The 1-, 3-, and 5-year OS rates were 38.7%, 19.8%, and 15.5% in the 60-69-year group, 23.9%, 7.75%, and 4.70% in the 70-79-year group, and 11.8%, 2.59%, and 1.00% in the 80-89-year group. Among patients aged ≥ 90 years, these rates fell markedly to 4.85%, 0.21%, and 0.07%, respectively (P < 0.001) (Fig. 3B).

Outcomes by time period of older AML

We next analyzed the survival outcomes of older AML patients by time period. Results showed a steady prolongation of median OS, from 2 months (95% CI: 2–2) during 2000–2008, to 3 months (95% CI: 3–3) in 2009–2016, and further to 4 months (95% CI: 4–4) in 2017–2021. Long-term survival rates analysis also revealed significant improvements. The 1-year OS rate rose from 19.6% (95% CI:18.9–20.2%) in 2000–2008 to 24.8% (95% CI:24.2–25.4%, 2000–2008 vs 2009–2016, P < 0.0001 ) in 2009–2016, and reached 29.6% (95% CI: 28.8–30.4%, P < 0.0001, 2009–2016 vs 2017–2021) in 2017–2021. The 3-year OS rate also progressively escalated from 7.27% (95% CI: 6.87–7.70%) to 9.80% ((95% CI: 9.38–10.2%, 2000-2008vs 2009–2016, P < 0.0001) and further to 13.4% (95% CI: 12.7–14.1%, 2009–2016 vs 2017–2021, P < 0.0001). Notably, the 5-year OS rate demonstrated a nearly two-fold increase, starting at 5.01% (95% CI: 4.67–5.37%) in 2000–2008, advancing to 7.13% (95% CI: 6.77–7.51%, P < 0.0001) during 2009–2016, and ultimately attaining 9.79% (95% CI: 8.98–10.70%, P < 0.0001) in the 2017–2021 cohort (Fig. 4).

Additionally, we also assessed survival outcomes among older AML patients stratified by age subgroups across 3 time periods. Among patients aged 60–69 years, the 1-year OS rate increased from 34.9% in 2000–2008 to 38.5% in 2009–2016, and to 43.0% in 2017–2021 (P < 0.0001). Consistent improvements were also observed in 3- and 5-year OS rates (P < 0.0001), reaching 24.4% and 20.3%, respectively, in 2017–2021 (Fig. 5A). In the 70–79 age group, the 1-, 3-, and 5-year OS rates also showed marked improvements, rising from 18.1%, 5.64%, and 3.43% during 2000–2007 to 30.1%, 11.1%, and 7.07% during 2017–2021(Fig. 5B). Although the baseline survival rate was relatively low in patients aged 80–89 years, a significant upward trend was observed. The 1-year OS rate climbed from 8.85% in 2000–2008 to 12.2% in 2009–2016, and further surpassed 15.5% in 2017–2021, representing an approximate doubling over the study period (Fig. 5C). Among patients aged ≥ 90 years, no statistically significant differences were observed in 1-year (3.32% vs 3.86%, P > 0.05) and 3-year OS rates (0.48% vs 0.36%, P > 0.05) between the 2000–2008 and 2009–2016 periods. However, a significant breakthrough was achieved in 2017–2021, with the 1-year OS rate rising to 7.97% and the 3-year OS rate reaching 1.96% (P = 0.005 for 2000–2008 vs 2017–2021; P = 0.016 for 2009–2016 vs 2017–2021) (Fig. 5D).

Outcomes of older patients with CBF AML

This study further evaluated the prognosis of older patients with CBF AML. Survival analysis demonstrated that older CBF AML patients had significantly worse OS than younger patients, with a median OS of 7 months versus 236 months and 5-year OS rate of 20.3% versus 64.1% (P < 0.001) (Fig. 6A). Subgroup analysis showed that in the older cohort, the inv(16)/t(16;16) subgroup had a longer median OS (9 months vs 6months) and higher 5-year OS rate (27.2% vs 16.2%) than the t(8;21) subgroup (P = 0.007) (Fig. 6B). Stratified by time period, compared to 2009–2016, the era of targeted therapy (2017–2021) did not significantly improve long-term survival in older t(8;21) patients (3-year OS rate 22.7% vs. 24.4%, P = 0.646) (Fig. 6C). In contrast, the inv(16)/t(16;16) subgroup showed significant survival improvement, with the 3-year OS rate increasing from 26.3% to 41.9% (P = 0.040) (Fig. 6D).

Causes of death

Subsequently, we evaluated the causes of death among older AML patients between 2000 and 2021. Overall, leukemia was the most common cause of death, accounting for 80.9% (34,688/42,901), followed by secondary malignancies (2,960/42,901, 6.9%) and other diseases (2,982/42,901, 7.0%) (Fig. 7). Among patients who succumbed to secondary malignancies, the majority were due to other hematologic malignancies, accounting for 5.9% of total deaths, primarily including myelodysplastic/myeloproliferative neoplasms (MDS/MPN) (1,733/42,901, 4.0%), non-Hodgkin lymphoma (423/42,901, 1.0%), while non-hematologic malignancies accounted for only 1.3%. When analyzed in five-year intervals, we observed a gradual decline in the proportion of deaths due to leukemia, decreasing from 81.6% in the first 5-year period to 49.1% in the second 5-year period, and further dropping to 21.5% in the third 5-year period. In contrast, the proportions of deaths due to secondary malignancies, cardio-cerebrovascular diseases, and other diseases increased from 6.8%, 2.6%, and 6.48% in the first 5-year period to 11.8%, 12.7%, and 47.3% in the third 5-year period (P < 0.001, Fig. 7). These findings indicate that leukemia was the predominant cause of death within the first 5 years after diagnosis. However, among patients who survived more than 10 years after diagnosis, other diseases (47.3%) and late relapse of leukemia (21.5%) became the most common causes of death, followed by cardio-cerebrovascular diseases (12.7%) and secondary malignancies (11.8%).

Based on large-scale, real-world data from the SEER database, this study systematically analyzed the evolution of epidemiological characteristics, clinical features, and survival outcomes of older patients with AML in the targeted therapy era.

Our findings confirm a pronounced age-dependent pattern in AML epidemiology. Between 2000 and 2021, the incidence of AML rose steadily among individuals aged ≥ 60 years, while remaining stable in younger cohorts (< 60 years). The annual age-adjusted incidence rate increased significantly after age 60, peaking in the 80–84 years age group (21.82–30.24 per 100,000), which is approximately 20-fold higher than that in individuals under 60 (1.29–1.54 per 100,000). This trend is consistent with previous reports [13, 25–27], and our study, with its larger sample size, provides stronger validation. It can be inferred that the incidence of AML in older adults will continue to rise as global population aging accelerates.

Clinically, older AML patients were significantly more likely to present with non-AML as their first primary malignancy than those younger counterparts, suggesting a higher prevalence of secondary AML in the older patients. Furthermore, according to the 2016 WHO classification, we observed a a greater proportion of AML-MRC among older patients. Notably, the proportion of t-MN was unexpectedly lower in older AML patients than in younger ones and decreased progressively with advancing age. However, previous studies indicate that t-AML accounts for approximately 7–8% of all AML cases and occurs mainly in older individuals[28]. Several factors may explain this discrepancy. First, older patients are less likely to receive intensive chemo-/radiotherapy for prior malignancies (whether hematologic or solid), potentially reducing their risk of t-MN. Second, as t-MN encompasses both therapy-related MDS and AML[29], the inherent limitations of the SEER database, which is impossible to independent classification, may introduce bias into the prevalence estimates.

CBF-AML typically occurs in younger patients, accounting for approximately 10–15% of newly diagnosed AML cases, but only about 5% in patients over 60[30]. Our data support the significantly lower incidence of CBF-AML among older patients, although potential under-reporting due to incomplete genomic testing in the SEER database cannot be excluded. Despite CBF-AML is generally considered a chemotherapy sensitive subtype with favorable risk[31–32], most older patients are unfit for intensive regimens, resulting in poorer outcomes than younger counterparts. We observed that the introduction of targeted therapies has significantly improved survival in older patients with inv(16)/t(16;16), but not in those with t(8;21). This disparity may be related to the widespread clinical use of the venetoclax plus azacitidine (VA) regimen. Based on currently limited data from a study of 30 newly diagnosed CBF-AML patients unfit for chemotherapy, the inv(16)/t(16;16) subtype demonstrated an outstanding response rate to VA regimen, with a CR/CRi rate of 100%. In contrast, the t(8;21) subtype showed a significantly lower CR/CRi rate of only 31%[33]. Although the sample size was small, these findings suggest that the VA regimen may be an effective therapeutic option for inv(16)/t(16;16) AML patients, whereas patienys with t(8;21) likely derive limited benefit. Therefore, further studies are needed to evaluate the long-term efficacy of VA in older CBF-AML patients unfit for intensive chemotherapy.

Earlier analyses from the SEER database showed OS rates increased for each successive decade (1977–1986, 1987–1996, 1997–2006) in patients aged 65–74 years, but no improvement in those 75 years and older[25]. Our study demonstrated that OS improved significantly across all age groups of older AML patients in the targeted therapy era (2017–2021), with particularly notable enhancements in 1-year OS. Remarkably, even the super-elderly group (≥ 90 years) showed clear benefits. Although targeted therapy improved the survival outcomes of older AML patients in the real world, the median OS remains short (60–69 years: 9 months; 70–79 years: 5 months; 80–89 years: 2 months; ≥90 years: 1 month), and 3-year OS rates remain low (60–69 years: 24.4%; 70–79 years: 11.1%; 80–89 years: 4.75%; ≥90 years: 1.96%). Furthermore, leukemia-related death persists as the predominant cause of death within five years of diagnosis. To address these challenges, multi-target combination strategies based on molecular profiling are being actively explored. Recent clinical trials targeting IDH1-mutated myeloid neoplasms (AML/MDS)[34] have demonstrated outstanding efficacy of a triple-regimen combining ivosidenib (IDH1 inhibitor) with venetoclax and azacitidine. The composite complete remission (CRc) rate reached 90%, with 63% of patients achieving minimal residual disease (MRD)-negative status. Median event-free survival (EFS) and OS extended to 36 and 42 months, respectively. Similarly, studies[35–36] have also confirmed that combining FLT3 inhibitors with venetoclax and HMAs yield exceptional efficacy in newly diagnosed FLT3-mutated AML patients, achieving CRc rates of 96–100% and approximately 70% 2-year OS rates. These advances provide new therapeutic paradigms for improving the long-term prognosis of older AML patients. Future management of older AML may require more precise and individualized treatment approaches.

Of course, the SEER database lacks critical clinical information such as details of specific treatment regimens (including targeted agent usage), cytogenetics, genomics, whether allogeneic hematopoietic stem cell transplantation (allo-HSCT), and key geriatric assessment metrics like comorbidity indices. Therefore, the findings of this study cannot fully reflect the impact of targeted therapies on survival outcomes. Future multi-center real-world studies are needed to further validate the improvement in survival conferred by targeted agents in older AML patients and to evaluate their long-term efficacy and safety.

In summary, this study represents the largest real-world analysis of oler AML to date. The results reveal a significant upward trend in the incidence of older AML, peaking in the 80–84 years age group. Notably, the occurrence of t-MN in older AML patients showed no significant difference compared to younger patients. In the targeted therapy era, survival has significantly improved for older AML patients, including the super-elderly (≥ 90 years). These findings provide critical evidence for the clinical management of older AML, but future large-scale real-world studies are needed for further validation.

Author contributions X.J.L designed the study, interpreted data, wrote and revised the manuscript. X.J.L, Z.Y.Z and J.W performed statistical analysis and wrote the manuscript. X.N and X.L.Z contributed to manuscript revision. All authors reviewed and approved the final manuscript.

Funding This study was supported by the 2022 Nanchong City-University Science and Technology Strategic Cooperation Project (Grant No. 22SXZRKX007) and the Scientific Research and Development Program Project of the Affiliated Hospital of North Sichuan Medical College (Grant No. 2024GC009).

Data availability The data that support the findings of this study are available in the SEER database.

Ethics approval and consent to participate This atricle based on the publicly available SEER database, and therefore did not require institutional review board approval.

Conflict of interest The authors declare no competing interests.

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The Outcome of Older Patients with Acute Myeloid Leukemia Based on the SEER Database in the Era of Targeted Therapy

Status:

Version 1

Abstract

Figures

Background

Materials and methods

Data source and patient selection

Statistical analysis

Results

Incidence of older AML patients

Clinical characteristics of older AML patients

The overall outcome of older AML patients

Outcomes by time period of older AML

Causes of death

Discussion

Conclusion

Declarations

References

Additional Declarations

Status:

Version 1

The Outcome of Older Patients with Acute Myeloid Leukemia Based on the SEER Database in the Era of Targeted Therapy

Status:

Version 1

Abstract

Figures

Background

Materials and methods

Data source and patient selection

Statistical analysis

Results

Incidence of older AML patients

Clinical characteristics of older AML patients

The overall outcome of older AML patients

Outcomes by time period of older AML

Causes of death

​​Discussion

Conclusion

Declarations

References

Additional Declarations

Status:

Version 1

Discussion