Decitabine Displays Comparable Outcomes, Improved Safety to Induction Chemotherapy in Older AML

Decitabine demonstrated a comparable overall survival and rate of hematopoietic stem cell transplant in addition to a lower incidence of adverse effects vs induction chemotherapy with daunorubicin and cytarabine in older patients at least 60 years of age with acute myeloid leukemia.

Decitabine demonstrated comparable rates of overall survival (OS) and hematopoietic stem cell transplant (HSCT) in addition to a lower incidence of adverse effects (AEs) vs induction chemotherapy with daunorubicin and cytarabine (Vyxeos) in older, fit patients at least 60 years of age with acute myeloid leukemia (AML), according to findings from the randomized phase 3 study (NCT02172872) presented at the 2022 EHA Congress.

The results revealed comparable OS rates across all landmark analyses, with a 4-year OS rate of 26% (95% CI, 21%-32%) in the decitabine arm vs 30% (95% CI, 24%-35%) in the induction chemotherapy arm (HR, 1.04; 95% CI, 0.86-1.26; P = .68).

“Decitabine provides a better tolerated alternative to aggressive chemotherapy in older, fit patients with similar transplant rates on protocol and subsequent transplant. We also saw fewer toxicities, shorter hospitalizations, and better quality of life,” lead study author Michael Lübbert, MD, hematologist at the University of Freiburg Medical Center in Freiburg, Germany said in a presentation of the data.

AML is largely diagnosed in older adults over 65 years of age who have a lower tolerance to conventional induction chemotherapy compared with younger patients. Despite treatment with induction chemotherapy, older patients with AML have poor long-term survival without curative HSCT.

Over the past decade, DNA-hypomethylating agents such as decitabine, although not curative as monotherapy, have been considered a safer alternative for patients who are unfit for induction chemotherapy. A prolonged 10-day course of decitabine has shown promising efficacy in prior studies with older patients with AML and may be a more suitable treatment before HSCT than induction chemotherapy in fit patients.

As such, the open-label study compared the efficacy and safety of 10-day decitabine with conventional 3+7 induction chemotherapy prior to HSCT in older patients with newly diagnosed AML.

The study enrolled 606 patients with newly diagnosed or de novo or secondary, untreated AML at least 60 years of age who were fit for intensive 3+7 chemotherapy. Patients must have had a white blood cell count of no more than 30 x 109/l at randomization. Patients were randomized 1:1 to intensive chemotherapy (n = 303) or a 10-day course of decitabine monotherapy (n = 303) before proceeding to allografting.

Patients with at least stable disease and a human leukocyte antigen–matched donor were encouraged to undergo HSCT after at least 1 treatment cycle.

Decitabine maintenance was only administered in patients who did not undergo allografting in the decitabine arm.

The primary end point was OS, with secondary end points of complete response (CR)/CR with incomplete count recovery (CRi), progression-free survival, disease-free survival, transplantation rate and outcome, safety, health economics including hospitalizations and supportive care, and quality of life.

Regarding baseline characteristics, most patients in the decitabine and chemotherapy arms were between the ages of 65 and 69 years, had an ECOG performance status of 0, had intermediate-risk disease per European LeukemiaNet 2017 stratification, and had normal karyotype.

NPM1 mutations were present in 23% of patients in the decitabine arm vs 14% of patients in the chemotherapy arm; TP53 mutations were present in 18% of patients in each arm.

In terms of treatment exposure, most patients received between 2 (25%) and 3 (21%) cycles of decitabine vs 1 (39%) and 2 (38%) cycles of chemotherapy.

Additional results demonstrated 1-, 2-, and 3-year OS rates in the decitabine and chemotherapy arms, respectively, of 58% (95% CI, 52%-63%) and 59% (95% CI, 54%-65%); 37% (95% CI, 32%-43%) and 40% (95% CI, 35%-46%); and 30% (95% CI, 25%-36%) and 33% (95% CI, 28%-38%).

The 4-year incidence of relapse or progressive disease was 57% with decitabine vs 51% with chemotherapy, and the 4-year incidence of treatment-related mortality was 21% vs 25%, respectively.

Subgroup analysis indicated that chemotherapy elicited improved OS in patients between the ages of 60 and 69 years, with favorable- or intermediate-risk disease, NPM1 mutations, and negative monosomal karyotype.

Lübbert emphasized that patients aged at least 70 years of age or older had improved OS with decitabine (HR, 0.84; 95% CI, 0.55-1.26), whereas patients between the ages of 60 and 64 years (HR, 1.34; 95% CI, 0.79-2.28) and those with NPM1 mutations (HR, 2.0; 95% CI, 0.96-4.17) had shorter OS with decitabine.

Notably, the rate of HSCT was the same between arms, at 52%. In the decitabine arm, 40% and 12% of patients received HSCT on- and off-protocol, respectively. In the chemotherapy arm, these rates were 39% and 13%, respectively.

The 1-, 2-, 3-, and 4-year OS rates from on-protocol HSCT in the decitabine and chemotherapy arms, respectively were 66% (95% CI, 56%-73%) and 75% (95% CI, 66%-81%); 56% (95% CI, 47%-65%) and 58% (95% CI, 49%-67%), 50% (95% CI, 41%-59%) and 51% (41%-60%), and 45% (95% CI, 35%-55%) and 47% (95% CI, 37%-56%).

The 4-year incidence of progression was 24% with decitabine vs 22% with chemotherapy, and the 4-year incidence of treatment-related mortality was 31% vs 33%, respectively.

A higher percentage of patients in the chemotherapy arm achieved CR/CRi (67%; on-protocol, 61%; off-protocol, 6%) vs those in the decitabine arm (60%; on-protocol, 48%; off-protocol, 13%).

However, fewer patients in the decitabine arm had grade 3 to 5 AEs vs those in the chemotherapy arm during treatment. Specifically, treatment with decitabine led to a lower rate of common toxicities including blood and lymphatic disorders, infections, and gastrointestinal disorders, although the incidence of grade 5 treatment-related AEs after HSCT was 25% (n = 122) with decitabine vs 22% (n = 118) with chemotherapy.

Furthermore, health economics, which was assessed during the first 3 cycles of protocol therapy in a subset of 173 patients, demonstrated decitabine led to improvements in days of hospitalization (P = .007), need of intravenous antibiotics (P < .001), and red blood cell (P = .024) and platelet (P < .001) transfusions.

“The strategy of bridging to transplant [with decitabine] is well feasible in this European trial network of experienced centers,” Lübbert concluded.


Lübbert M, Wijermans P, Kicinski M, et al. 10-day decitabine versus conventional chemotherapy (“3+7”) followed by allografting in AML patients ≥60 years: a randomized phase III study of the EORTC Leukemia Group, CELG, GIMEMA and German MDS Study Group. Presented at: EHA 2022 Hybrid Congress; June 9-12, 2022; Vienna, Austria. Abstract S125.