Alternating Clofarabine, Low-Dose Cytarabine with Decitabine Promising in Older AML Patients

Prolonged treatment with a rotating regimen of clofarabine plus low-dose cytarabine and decitabine is well tolerated and effective in acute myeloid leukaemia patients of 60 years or older

medwireNews: Older patients with acute myeloid leukaemia (AML) can benefit from prolonged treatment with a low intensity regimen of clofarabine and low-dose cytarabine alternating with decitabine , according to the final analysis of a phase II trial.

After induction with open-label clofarabine (20 mg/m2) and low-dose cytarabine (20 mg twice a day), patients who responded underwent consolidation therapy comprising three cycles of the combination treatment alternating with an equal number of decitabine (20 mg/m2) cycles for up to 18 cycles.

Of the 118 treatment-naive AML patients aged 60 years or older included in the study, 71 (60%) achieved complete remission (CR), defined as less than 5% blasts in the peripheral blood and bone marrow, a peripheral absolute neutrophil count of at least 1 x 109/L and a platelet count above 100 x 109/L. And eight (7%) achieved complete remission with incomplete platelet recovery.

Median overall survival (OS) across the entire study population was 11.1 months. But median OS varied significantly between patients who achieved a response (either CR or CR with incomplete platelet recovery) and those who did not, at 18.5 versus 4.2 months.

After a median follow-up of 41.4 months, median relapse-free survival for participants exhibiting a response was 14.1 months, which the researchers say “compares very favorably to data from previous trials of hypomethylating agents in this setting”.

When patients were stratified by karyotype, the CR rate was 71% for the 38% of patients who had a normal or diploid karyotype. This compared with a 50% CR rate in the 41% of participants considered to have an adverse-risk karyotype.

And multivariate analysis showed that an adverse karyotype and a white blood cell count higher than 10 x 109/L were the only two factors significantly associated with a poor OS.

The most frequent adverse event of grade 3 or 4 was febrile neutropenia, occurring in 61% of participants, followed by infections, elevated levels of transaminases, bilirubin and creatinine, and rash in respectively 41%, 11%, 5%, 3% and 2% of the study population.

“The lower intensity approach of this regimen is exemplified by the low early death rates at 4 and 8 weeks of 3% and 7%, respectively”, say Tapan Kadia, from The University of Texas MD Anderson Cancer Center in Houston, USA, and co-authors.

They conclude in Cancer: “Further studies expanding this strategy and prospectively comparing it with existing higher and lower intensity therapies in older adults are needed.”


Kadia TM, Faderl S, Ravandi F, et al. Final Results of a Phase 2 Trial of Clofarabine and Low-Dose Cytarabine Alternating With Decitabine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia.Cancer 2015; Advance online publication 25 March. doi:10.1002/cncr.29367

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