Outcomes and Prognostic Scoring System for Elderly Patients with Acute Myeloid Leukemia

Background: The prognosis of elderly patients with acute myeloid leukemia (AML) remains poor. Elderly patients are frequently intolerant to intensive chemotherapy due to poor performance status and co-morbidities. Moreover, considering the increase of genetic abnormalities, it is disputable whether conventional chemotherapy improves the prognosis of elderly AML patients. The purpose of this study is to identity patients who would benefit from conventional chemotherapy.

Patients and Methods: We retrospectively analyzed the outcome of patients with AML aged over 65 years who received conventional chemotherapy based on the JALSG GML 200 protocol at our institution between December 2011 and January 2020. Patients with acute promyelocytic leukemia were excluded. No patients underwent hematopoietic cell transplantation (HCT). Dose reduction of each regimen was considered in patients over 70 years of age. MEC regimen was used for reinduction therapy in 70% of patients with induction failure. The primary end point was overall survival (OS) after induction therapy. Factors associated with the achievement of complete remission (CR) and overall mortality were analyzed using logistic regression and Cox proportional hazards models, respectively.

Results: A total of 74 patients were analyzed. The median age was 72.8 years (range, 65-85). Nine patients (12%) had an ECOG performance status of 3-4. The most common AML subtype was AML with myelodysplasia-related changes (n=30, 41%) followed by AML with maturation (n=11, 15%). Twenty patients (27%) were previously diagnosed with myelodysplastic syndromes (MDS). According to the 2017 ELN stratification, 3 patients (4%) were classified as favorable-risk, 44 (60%) as intermediate-risk, and 27 (37%) as adverse-risk. Overall, 21 patients (28%) achieved CR after induction therapy. Among 53 patients with induction failure, 37 received reinduction therapy and 14 (38%) achieved CR. The ELN favorable- or intermediate-risk (OR, 23.2; 95% CI, 4.59-117.0, p<0.001) and age under 70 years (OR, 7.62; 95% CI, 1.54-37.8, p=0.013) were important factors associated with the achievement of CR. Median OS was 10.3 months for all patients and 19.3 months for patients who achieved CR after induction therapy. The probability of 3-year survival was 20.9% in the total patients. The day 100 and 1-year NRM incidences were 4% and 8%, respectively. In multivariate analysis, lower performance status (3-4) (HR, 3.93; 95% CI, 1.81-8.49, p<0.001), age 70 and older (HR, 3.38; 95% CI, 1.76-6.47, p<0.001), the ELN adverse-risk (HR, 3.16 95% CI, 1.83-5.47, p<0.001), and previous MDS diagnosis (HR=2.36, 95% CI=1.29-4.30, p<0.001) were the significant independent prognostic factors for poor OS. On the basis of the number of these four factors, the prognostic score was calculated for each patient and patients were categorized into five groups (score 0-4). The score was significantly correlated with OS (p<0.001, Figure). The probability of 1-year survival was 85.7% for score 0, 59.4% for score 1, and 5.9% for score 2. All patients for score 3 and 4 died within 1 year and their median OS was 2.8 months for score 3 and 0.4 months for score 4.

Conclusions: Each two patient (age, performance status) and disease (ELN disease risk, history of MDS) factors were significantly associated with survival in elderly patients with AML. The prognostic scoring system based on the four factors clearly stratified survival, suggesting that it will be useful for making a treatment decision. Further large-scale studies are required to validate this system and a combination therapy with molecular targeted drugs should be established for patients with poor prognosis.