Evaluating a Risk-Adapted Treatment Approach in Younger Patients With AML

A risk-adapted approach incorporating minimal residual disease (MRD) and cytogenetic data could help identify patients with acute myeloid leukemia (AML) who would benefit from hematopoietic cell transplantation (HCT), or who would be able to avoid autologous HCT (AHCT), according to results from a phase II trial presented at the 22nd Congress of the European Hematology Association.

Adriano Venditti, MD, from the University of Rome Tor Vergata in Italy, and researchers evaluated the feasibility of this approach in the GIMEMA AML1310 trial, which assigned risk and post-remission therapy according to patients’ pre-treatment cytogenetic data and post-consolidation levels of MRD.

Between January 2012 and May 2015, investigators enrolled 515 patients with previously untreated AML from 55 institutions. At baseline, patients were categorized as low risk (core binding factor [CBF]-positive AML without c-Kit mutations or NPM1-positive, FLT3-negative AML), intermediate risk (FLT3-TKD mutated, c-Kit mutated, or CBF-positive AML), or high risk (adverse-risk karyotype, FLT3-ITD mutations).

Dr. Venditti presented results from 500 patients (median age = 49 years; range = 18-61 years) who were evaluable for response at the time of presentation. Most patients (73%) had intermediate-risk disease; 11 percent had low-risk disease, and 16 percent had high-risk disease.

Patients received the following induction therapy:

  • intravenous daunorubicin 50 mg/m2 once-daily on days 1, 3, and 5
  • intravenous etoposide 50 mg/m2 once-daily on days 1-5
  • intravenous cytarabine 100 mg/m2 as a once-daily continuous infusion on days 1-10

Those who achieved a complete remission (CR) or CR with incomplete platelet recovery (CRi) after one or two induction cycles then received consolidation therapy with daunorubicin (50 mg/m2 once-daily on days 4-6) and cytarabine (500 mg/m2 twice-daily on days 1-6). Patients who did not achieve CR/CRi received salvage therapy with fludarabine, cytarabine, and idarubicin.

MRD was assessed by flow cytometry after consolidation therapy, and patients received HCT within 3 months of the end of consolidation therapy. Patients who had high-risk disease and/or were MRD-positive were assigned to receive allogeneic HCT (alloHCT), and those who had low-risk disease and/or were MRD-negative were assigned to receive AHCT.

Following induction therapy, 361 of 494 evaluable patients achieved CR (73%); 18 percent had refractory AML and 9 percent died during treatment. Subsequently, 341 patients completed the consolidation phase and were allocated to receive transplant and a total of 232 patients eventually received transplant (109 [33%] AHCT and 123 [36%] alloHCT).

After a median follow-up of 27.9 months (range not provided), the cumulative incidence of relapse was 32.9 percent.

The 24-month overall survival (OS) and disease-free survival (DFS) rates were 55.9 percent and 54.9 percent, respectively (74.8% and 63.8% in the low-risk group; 42.5% and 44.8% in the high-risk group).

In the intermediate-risk category, rates of OS and DFS were similar, regardless of MRD status:

  • MRD-negative: 78.6% and 61.4%
  • MRD-positive: 69.8% and 66.6%

“In the intermediate-risk category, HCT can be avoided if MRD is not detectable,” the researchers noted. “If MRD is positive, HCT can prolong OS and DFS to equalize those of the low-risk category.”

The results suggest that “a program of risk-adapted, MRD-driven therapy is feasible in a multicenter, cooperative setting,” the authors concluded.

The study’s findings are limited by the lack of a comparator arm and that not all patient allocated to a treatment approach received that treatment.

The authors report no relevant conflicts of interest.


Venditti A, Piciocchi A, Candoni A, et al. Risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukemia: results of the AML1310 trial of the GIMEMA Group. Abstract #S111. Presented at the 22nd Congress of the European Hematology Association, June 23, 2017; Madrid, Spain.