ATLANTA — Induction therapy with either idarubicin plus cytarabine plus etoposide (ICE), or idarubicin plus etoposide followed by azacitidine (AZA-after), yielded comparable rates of complete remission (CR) among patients with high-risk acute myeloid leukemia (AML), according to a study presented during the 54th American Society of Hematology (ASH) Annual Meeting and Exposition.

Both regimens appear to be “equally effective in producing CR in patients with AML who are not candidates for genotype-adapted treatment approaches,” reported lead author Richard F. Schlenk, MD, of the University of Ulm in Germany, who with his colleagues reported the first results of a randomized, phase 2 study.

Prognosis is “generally poor” for the approximately 33% of AML patients who are not candidates for genotype-adapted treatment, researchers noted. These patients include those with no PML-RARA, CBFB-MYH11, RUNX1-RUNX1T1, NPM1 or activating FLT3 mutations. Many have myelodysplasia-related changes or AML with recurrent cytogenetic abnormalities, while others have cytogenetically normal AML (CN-AML) with wild-type NPM1 and FLT3.

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Azacitidine is active when AML has low blast counts, which is common in AML with myelodysplasia-related changes or CN-AML.

Dr. Schlenk and colleagues sought to evaluate the clinical efficacy of azacitidine in combination with intensive induction chemotherapy and in maintenance for two years as a single agent in patients with AML who are not candidates for genotype-adapted therapy.

A total of 104 patients between 18 and 82 years (median age 62.5 years) without specific genetic mutations were randomized for standard ICE induction therapy (idarubicin 12 mg/m2 on days 1,3 and 5; cytarabine 100 mg/m2 on days 1-7; etoposide 100 mg/m2 on days 1-3) or one of three experimental study arms: 1) AZA-prior, azacitidine  (100 mg/m2 subcutaneous (SQ) or 15 min. IV per day, on days 1-5) plus idarubicin (12 mg/m2 IV per day on days 6, 8 and 10), plus etoposide (100 mg/m2 IV per day, on days 6-8); 2) AZA-concurrent, azacitidine (100 mg/m2 per day SQ or 15 min. IV, on days 1-5) plus idarubicin (12 mg/m2 per day IV on Days 1,3, and 5) plus etoposide 100 mg/m2 IV per day, on days 1, 2 and 3; or 3) AZA-after, idarubicin (12 mg/m2 per day IV on days 1, 3 and 5) plus etoposide (100 mg/m2 per day IV, on days 1,2 and 3) plus azacitidine (100 mg/m2 per day SQ or 15 min. IV, on days 4-8). Dose reduction for idarubicin and etoposide was employed for patients aged >65 years.

 “The number of responding patients in the treatment arms AZA-prior and AZA-concurrent after the first stage of the study were 11 of 26 (42%) and 10 of 26 (38%),” the authors reported. ICE-arm patients had a CR rate of 61.5% and AZA-after-arm patients had a CR rate of 54% (P=0.34).

At a median followup of 10.6 months, no differences were evident in overall survival rates.

Following two cycles of induction therapy, participants achieving complete remission underwent consolidation therapy with allogenic hematopoietic blood stem-cell transplantation (HSCT) from matched donors (first priority) or three courses of high-dose cytarabine followed by 2-year maintenance with azacitidine monotherapy (second priority).

“The most frequent serious adverse events (SAEs) were grade 3/4 infections with an overall incidence of 25% and ranging from 20 to 34% in the different treatment arms,” Dr. Schlenk noted. “There were no relevant differences in the number of SAEs across the four treatment arms.”

“Intensive induction treatment with idarubicin and etoposide with prior or concurrent azacitidine resulted in lower CR rates,” he concluded.