Abstract
The outcome of acute myeloid leukemia patients aged 70 years or older is poor. Defining the best treatment option remains controversial especially when choosing between intensive chemotherapy and hypomethylating agents. We set up a multicentric European database collecting data of 3 700 newly diagnosed acute myeloid leukemia patients ≥70 years. The primary objective was to compare overall survival in patients selected for intensive chemotherapy (n = 1199) or hypomethylating agents (n = 1073). With a median follow-up of 49.5 months, the median overall survival was 10.9 (95% CI: 9.7–11.6) and 9.2 months (95% CI: 8.3–10.2) with chemotherapy and hypomethylating agents, respectively. Complete remission or complete remission with incomplete hematologic recovery was 56.1% and 19.7% with chemotherapy and hypomethylating agents, respectively (P < 0.0001). Treatment effect on overall survival was time-dependent. The Royston and Parmar model showed that patients treated with hypomethylating agents had a significantly lower risk of death before 1.5 months of follow-up; no significant difference between 1.5 and 4.0 months, whereas patients treated with intensive chemotherapy had a significantly better overall survival from four months after start of therapy. This study shows that intensive chemotherapy remains a valuable option associated with a better long-term survival in older AML patients.
Highlights
The prognosis of acute myeloid leukemia (AML) patients aged ≥70 years is poor
Patients treated with semi-intensive chemotherapy (n = 464), LDAC (n = 127) or supportive care (n = 837) were not included in the primary analysis
The study population for the principal objective of this study included 1 199 patients treated with intensive chemotherapy (IC) and 1 073 patients treated with hypomethylating agents (HMAs)
Summary
The prognosis of acute myeloid leukemia (AML) patients aged ≥70 years is poor. A minimal data set was collected for each patient, including the variables age, sex, date of diagnosis, AML status (de novo or secondary), white blood cell count, percentage of peripheral and bone marrow blasts, LDH, cytogenetic risk, NPM1, FLT3-ITD, CEBPA, IDH1, IDH2 mutational status, nature of first-line therapy, response to treatment, allogeneic hematopoietic stem cell transplantation in first complete remission, date of relapse and/or death. Multivariate analyses included HMAs vs IC together with potential confounding factors [age ≥75 y, performance status >1, white blood cell count at diagnosis >30 giga per liter, cytogenetic risk, secondary vs de novo AML, NPM1 mutation, FLT3-ITD mutation (for RFS) and study period]. Covariates were all variables expected to be associated with HMAs vs IC in clinical practice (age, performance status, WBC, cytogenetic risk, secondary vs de novo AML, NPM1 and FLT3-ITD mutations, study period and center).
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