Adding clofarabine to standard induction therapy shows no effect on survival for patients with newly diagnosed acute myeloid leukemia (AML), according to a study published in Blood.
Standard induction treatment with cytarabine and an anthracycline has shown to result in high rates of complete remission in patients with AML. However, a high frequency of relapse is also documented, especially in adults aged < 65 years (50% relapse rate). Clofarabine, a second-generation nucleoside analog with demonstrated anti-leukemic activity in older adults, had yet to be assessed in younger and middle-aged adults.
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Researchers led by Bob Löwenberg, MD, PhD, Erasmus University Medical Center (Netherlands), conducted a phase III study that compared two different induction regimens, idarubicine-cytarabine and amsacrine-cytarabine with (n = 393) or without (n = 402) clofarabine, in patients aged 18 to 65 years. Event-free survival was the primary endpoint for the study, and toxicities were assessed as well.
Results of the study showed no differences in overall survival or event-free survival between the two arms after a median follow-up of 36 months. Cumulative 4-year probabilities for competing risk of death were greater in patients in the clofarabine group (22% versus 15%, respectively). Treatment with clofarabine resulted in added grade 3-4 toxicities and delayed hematologic recovery. Researchers also noted no difference in the benefit of clofarabine schedule according to patient age (younger than 45 years versus 45-60 years versus 61-65 years).
Clofarabine did have positive effects on early complete remission and relapse rates. Patients in the clofarabine group had an improved relapse rate compared with patients not in the group (35% versus 44%, respectively). However, researchers concluded that, “Overall the disadvantages of the enhanced toxicities offset the advantages of a reduction of relapse so that ultimately there is no overall net benefit in survival in the broad population of patients with AML.”
Additional studies are required to exploit the advantages of clofarabine with a less-toxic treatment course in first-line therapy for patients with AML.
