In a nutshell
This study aimed to investigate the effects of valproate (Depakene) and all-trans retinoic acid (ATRA) in treatment-naive elderly patients with acute myeloid leukemia.
This study concluded that the addition of ATRA to decitabine (Dacogen) chemotherapy led to a higher remission rate and survival extension in these patients, without increasing toxicity.
Some background
Valproate is used to treat epilepsy and bipolar disorder and prevent migraine headaches. It is known as a histone deacetylase inhibitor. All-trans retinoic acid (ATRA) mocks the function of vitamin A1 and allows for growth and development. It is known as a differentiation inducer. Decitabine is used as a chemotherapy for myelodysplastic syndromes and for acute myeloid leukemia. It is known as a DNA-hypomethylating agent.
Epigenetic therapy is the use of drugs or other epigenome-influencing techniques to treat medical conditions. Epigenetics relates to non-genetic changes in gene expression. DNA-hypomethylating agents are studied in combination with other epigenetic drugs, such as histone deacetylase inhibitors or differentiation inducers, in myeloid neoplasias.
It was not known what the effect of valproate and ATRA were in previously not treated elderly patients with acute myeloid leukemia (AML).
Methods & findings
This study involved 200 patients with AML. Patients had an average age of 76 years who were not previously treated. Patients were split into 4 groups. 47 patients received decitabine alone (DEC group). 57 patients received decitabine in combination with valproate (DecVal group). 46 patients received ATRA alone (ATRA group). 50 patients received ATRA in combination with valproate (ATRAVal group). The main outcome measured was complete and partial remissions. Other outcomes measured were overall survival (OS), event-free survival (EFS), progression-free survival (PFS) and safety. Patients were followed up for an average of 25.1 months.
The remission rate was 21.9% when ATRA was added compared to 13.5% without ATRA. ATRA resulted in an 80% improvement in the chance of remission. The addition of valproate did not influence the remission rate. It was 17.8% with valproate and 17.2% without valproate.
The average OS was 8.2 months with ATRA compared to 5.1 months without ATRA. Improved survival was observed and was associated with a longer response duration. With valproate, no survival difference was observed.
Side e effects were mainly hematologic (relating to blood), without relevant differences between the 4 groups.
The bottom line
This study concluded that the addition of ATRA to decitabine led to higher remission rate and survival extension in previously not treated elderly patients with AML, without an increase in side effects.
The fine print
The study included a small number of participants. Larger studies are needed.
What’s next?
Consult your physician about treatment options for AML.
Published By :
Journal of clinical oncology
Date :
Dec 03, 2019
