Decitabine ‘better-tolerated alternative’ to chemotherapy for older, fit patients with AML
Click Here to Manage Email Alerts
Older, fit patients with acute myeloid leukemia who received decitabine had transplant and survival rates comparable to those treated with induction chemotherapy but with fewer toxicities, according to results of a randomized phase 3 study.
“Ten-day decitabine provides a better-tolerated alternative to aggressive chemotherapy in older, fit patients with AML,” Michael Lübbert, MD, of the division of hematology, oncology and stem cell transplantation at University of Freiburg Medical Center in Germany, said during a press briefing at European Hematology Association 2022 Hybrid Congress.
Background and methods
Resistance to standard intensive chemotherapy remains a major issue in the treatment of older, medically fit patients with AML, who have poor long-term survival outcomes without hematopoietic stem cell transplantation following induction chemotherapy, Lübbert said. DNA-hypomethylating agents (HMAs), including decitabine, represent a milder, potentially safer AML therapy and have been approved for medically unfit patients.
“The purpose of this study was to compare extended decitabine HMA monotherapy of 10 days to standard induction chemotherapy as bridges to allografting in fit, older [patients with AML],” Lübbert said.
The open-label, multicenter European study included 606 patients aged 60 years or older (median age, 68 years; 57% men) with newly diagnosed AML deemed suitable for conventional 3 + 7 induction chemotherapy. Half of the patients received intensive chemotherapy with daunorubicin, dosed at 60 mg/m2 for 3 days, and cytarabine, dosed at 200 mg/m2 for 7 days, followed by up to three additional chemotherapy cycles. The other half received decitabine, dosed at 20 mg/m2 for 10 days consecutively in the first cycle and 10 days or 5 days in later cycles depending on response. Investigators encouraged all patients who had stable disease or better and an HLA-matched donor to undergo HSCT after more than one treatment cycle. Those in the decitabine group who did not receive HSCT could continue to receive the agent.
OS served as the primary endpoint. Researchers also sought to determine whether decitabine would result in reduced toxicity.
Median follow-up was 4 years.
Key findings
Similar proportions of patients in the decitabine and induction chemotherapy groups (52%) underwent HSCT.
At the time of clinical cutoff June 30, 2021, 423 patients had died.
Results showed similar OS for the decitabine and chemotherapy groups (HR = 1.04; 95% CI, 0.86-1.26; median, 15 months vs. 18 months). Lübbert reported OS rates of 58% with decitabine vs. 59% with chemotherapy at 1 year, 37% vs. 40% at 2 years, 30% vs. 33% at 3 years and 26% vs. 30% at 4 years.
However, the decitabine group experienced fewer toxicities, the most common of which included blood and lymphatic disorders, infections, changes in laboratory investigations and gastrointestinal disorders. The decitabine group had lower rates of pre-HSCT grade 3 or higher febrile neutropenia (37% vs. 57%), platelet decrease (24% vs. 32%), oral mucositis (2% vs. 10%) and diarrhea (1% vs. 8%), but a higher rate of neutrophil decrease (19% vs. 13%), than the chemotherapy group. The decitabine group had a lower 30-day mortality rate (3.6% vs. 6.4%) and a slightly higher rate of grade 5 treatment-related adverse events after HSCT (25% vs. 22%).
“Notably, less time in the hospital was spent with decitabine,” Lübbert said. “We observed an average reduction of hospitalizations by 20%.”
Next steps
When asked about the potential of the results to change practice and improve quality of life for patients with AML, Lübbert noted an approximately 33% increase in the transplant rate among patients aged 70 years or older who received decitabine vs. standard chemotherapy.
“In patients in this age group, often with adverse cytogenetics, there seems to be a benefit to combine the ‘non-curative’ treatment with a subsequent curative approach,” he said.
Collapse
Lübbert M, et al. Abstract S125. Presented at: European Hematology Association 2022 Hybrid Congress; June 9-12, 2022; Vienna.
Click Here to Manage Email Alerts