New options for older patients with AML

Blood cancers

By Tony James

20 Oct 2015

Newer hypomethylating agents like azacitidine offer hope for older patients with acute myeloid leukaemia, according to Professor Hervé Dombret from the University Hospital Saint-Louis in Paris.

“The current approach subdivides older patients into those capable of tolerating intensive chemotherapy, those who may only tolerate low-intensity therapy such as low-dose cytarabine or hypomethylating agents like azacitidine, decitabine or guadecitabine, and those who will only tolerate best supportive care,” he said.

Decitabine was approved in Europe for the treatment of AML in 2012. Azacitadine is thought to be close to European approval, following the results of a phase 3 study by Professor Dombret and international colleagues including Professor John Seymour from the Peter MacCallum Cancer Centre in Melbourne.

The study, reported in Blood (2015; 126: 291-300), recruited patients aged 65 or more with newly-diagnosed AML and >30% bone marrow blasts.

They were randomised to azacitadine or conventional care, pre-selected as either standard induction chemotherapy, low-dose cytarabine or best supportive care on the basis of age, performance status, comorbidities and local practice.

There was a trend to improved median overall survival with azacitadine (10.4 vs 6.5 months, p=0.10), and it was better tolerated than conventional chemotherapy.

“Overall survival with azacitadine was superior to intensive chemotherapy in some subgroups of patients, including those with adverse cytogenetics and other risk factors,” Professor Dombret said.

Trials of hypomethylating agents combined with other drugs such as vosaroxin and sorafenib are now in progress.

Professor Dombret described the challenges of conducting clinical trials in older AML patients, who averaged 75 years in the azacitadine study.

“The classic outcome of overall survival might not be the best measure in these patients,” he said.

“They often have a high level of comorbidity, they may die of other causes, and adherence with treatment can be poor.”

Quality of life is also an important issue given the short median survival times, with a need to strike the right balance between quality and quantity of life for the individual patient.

Heterogeneous patient groups, with widely varying attitudes to involvement in a clinical trial, as well as the heterogeneity of the disease, also make it challenging to perform unbiased studies.

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