What are the long-term benefits of Allo-HSCT in elderly patients with CR1 AML?

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment option for patients with acute myeloid leukemia (AML), but its application is limited by treatment-related toxicity and donor availability, especially in elderly patients
.

However, since the early 2000s, major improvements in transplantation procedures (eg conditioning regimens, graft-versus-host disease prophylaxis, surrogate donors) have significantly expanded the feasibility of allo-HSCT
.

Therefore, transplantation therapy is now an option for patients ≥70 years of age
.

At the same time, pre-transplant regimens have improved in recent years, expanding the use of intensive therapy to older patients who are adequately treated with this regimen
.

Therefore, AML patients aged >60 years can be treated with conventional allo-HSCT in the first complete remission (CR1)
.

However, prospective studies evaluating the efficacy of allo-HSCT in this age group are lacking, and its overall and specific cytogenetic/molecular subgroup benefit remains controversial
.

 Therefore, to confirm this question, the French Innovative Leukemia Organization (FILO) conducted a 10-year large, retrospective, real-world time-dependent analysis of AML patients over 60 years of age treated at seven centers
.

Study methods Patient inclusion criteria included: (1) aged between 60-70 years; (2) diagnosed with AML in 2007-2017; (3) achieved CR1 after 1 or 2 courses of intensive chemotherapy; (4) according to European Leukemia Network (ELN) 2010 classification as intermediate risk (IR) or unfavorable risk (UR)
.

 Induction chemotherapy for patients, including anthracycline-based (daunorubicin or idarubicin) and cytarabine-based (100 or 200 mg/m2 daily for 7 days) with or without lomo Sting
.

Consolidation chemotherapy was based on anthracyclines and low-dose subcutaneous cytarabine (50 mg/m2 every 12 hours for 5 days)
.

The impact of allo-HSCT was analyzed by three models: (1) time-dependent analysis; (2) multistate model; (3) Superlandmark model
.

Findings 1.
Patient Characteristics and Transplantation Rates A total of 507 patients (Table 1) with a median age of 65 years (range: 60-70 years) were included in the study, including 369 (73%) IR and 138 (27%) IR ) UR patients, of whom 203 (40%) underwent allo-HSCT (IR: 135 [36%; IR-1: 86/233; IR-2: 49/136], UR: 68 [ 49%])
.

Notably, transplant rates in patients over 65 years of age have increased over time (pre-2011: 11%; 2011-2013: 26%; post-2013: 35%), while transplant rates in younger patients remained stable ( Before 2011: 51%; 2011-2013: 52%; after 2013: 62%)
.

Of the 203 patients who received transplantation, 25 (12%), 153 (75%), and 25 (12%) received non-myeloablative, reduced-intensity, and myeloablative conditioning regimens, respectively
.

Table 12.
allo-HSCT as a time-related variable: univariate and multivariate analyses For the entire cohort, allo-HSCT as a time-related variable was associated with better 3-year recurrence-free survival (RFS) rates (allo-free vs allo: 19% vs.
51%; P<0.
001) and overall survival (OS) rate (no allo vs allo, 35% vs 56%; P<0.
001) were significantly associated (Table 2; Figure 1)
.

This was observed in both IR and UR subgroups and in both age groups (i.
e.
age ≤65 years or >65 years)
.

Table 2 Figure 1 Multivariate time-dependent Cox model showing that allo-HSCT was associated with a significantly lower risk of recurrence (73% risk reduction; HR [95% CI], 0.
27 [0.
19-0.
38]; P<0.
001), but not recurrence There was an increased risk of related death (NRM) (3-fold increased risk; HR [95% CI], 3.
03 [1.
57-5.
84]; P<0.
001)
.

After allo-HSCT, the risk of RFS (53% risk reduction; HR [95% CI], 0.
47 [0.
35-0.
62]; P<0.
001) and OS (44% risk reduction; HR [95% CI], 0.
56 [ 0.
42-0.
76]; P<0.
001) was significantly reduced
.

ELN risk, but not age, is an independent adverse risk factor for recurrence, leading to worse RFS and OS
.

3.
Multistate model analysis The predicted 5-year probabilities of maintaining CR1 in IR and UR patients without allo-HSCT were 8% and 1%, respectively
.

The predicted probabilities of 5-year CR1 (“no allo-CR” + “allo-CR”) were 29% and 20% for the IR and UR risk groups, respectively (Fig.
2A)
.

When considering event-free patients 1 year after CR1 ("allo-CR" or "no allo-CR"), the 5-year predicted probability of recurrence after allo-HSCT was 19%, and most patients (79%) remained in "allo-CR" CR” (Figure 2B, left)
.

In contrast, patients who did not receive transplantation had a predicted probability of 66% relapse within the next 4 years (Fig.
2B, right panel)
.

Figure 24.
Super landmark model analysis allo-HSCT significantly improved patients’ RFS (HR [95%CI], 0.
47 [0.
36-0.
62]; P<0.
001) and OS (HR [95%CI], 0.
54 [0.
40-0.
72] ]; P<0.
001)
.

CONCLUSIONS: This study showed that allo-HSCT significantly improved outcomes in elderly AML patients with CR1 fit
.

Patients who did not undergo allo-HSCT had very low long-term RFS (<10%), and this study supports allo-HSCT as the best treatment option for these patients
.

allo-HSCT improves outcomes in ELN IR and UR AML patients aged >60 years in CR1
.

Reference source: Raynier Devillier, Edouard Forcade, Alice Garnier, et al.
In-depth time-dependent analysis of the benefit of allo-HSCT for elderly patients with CR1 AML: a FILO study.
Blood Adv (2022) 6 (6): 1804–1812.
https://doi.
org/10.
1182/bloodadvances.
2021004435.
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