Standard induction therapy for fit elderly Acute Myeloid Leukemia (AML) patients consist of daunorubicin and cytarabine (DA). However, outcomes in this subgroup of patients remain unsatisfactory.
In an article in the American Journal of Hematology, Agnieszka Pluta from the Medical University of Lodz, Poland, and colleagues published results from their randomized phase II study conducted by the Polish Adult Leukemia Group (PALG). In this study, the efficacy and safety of DA combined with cladribine (DAC), a purine analogue, was compared with DA alone in newly diagnosed elderly AML patients eligible for intensive chemotherapy.
A total of 171 AML patients (median age = 66 years, range 60–79) were randomly assigned to receive either DAC (n = 86) or DA (n = 85).
The key results of the study were:
- Complete Remission (CR) after first induction in all evaluable patients (n = 64) in the DAC (n = 35) and DA arm (n = 29); 44% vs 34%, P = 0.19
- CR in patients aged 60–65 years in the DAC (n = 23) and DA (n = 10) arm; 51% vs 29%, P = 0.02
- CR in patients aged 60–65 years with good and intermediate karyotype in the DAC (n = 13) and DA (n = 4) arm; 69% vs 21%, P = 0.0032
- Median Overall survival (OS) in all patients in the DAC and DA arms; 8.6 vs 9.1 months, P = 0.64
- OS was longer in patients aged 60–65 years with good and intermediate karyotype in DAC arm compared to DA arm; P = 0.02
- Non-hematological and hematological toxicities were similar in the DA and DAC arms
- Death occurred in 17% and 23% of patients in the DA (n = 14) and DAC (n = 18) arms respectively; P = 0.19
In summation, DAC improved the outcomes of elderly AML patients aged 60–65 years with good and intermediate risk karyotype.
Intensive induction chemotherapy using anthracycline and cytarabine backbone is considered the most effective upfront therapy in physically fit older patients with acute myeloid leukemia (AML). However, outcomes of the standard induction in elderly AML are inferior to those observed in younger patients, and they are still unsatisfactory. As addition of cladribine to the standard induction therapy is known to improve outcome in younger AML patients. The present randomized phase II study compares efficacy and toxicity of the DAC (daunorubicin plus cytarabine plus cladribine) regimen with the standard DA (daunorubicin plus cytarabine) regimen in the newly diagnosed AML patients over 60 years of age. A total of 171 patients were enrolled in the study (DA, 86; DAC, 85). A trend toward higher complete remission (CR) was observed in the DAC arm compared to the DA arm (44% vs. 34%; P = .19), which did not lead to improved median overall survival, which in the case of the DAC group was 8.6 months compared to in 9.1 months in the DA group (P = .64). However, DAC appeared to be superior in the group of patients aged 60-65 (CR rate: DAC 51% vs. DA 29%; P = .02). What is more, a subgroup of patients, with good and intermediate karyotypes, benefited from addition of cladribine also in terms of overall survival (P = .02). No differences in hematological and nonhematological toxicity between the DA and DAC regimens were observed.