Charles Craddock, CBE, FRCP, FRCPath, DPhil of Queen Elizabeth Hospital, Birmingham, UK discusses the results of the RAvVA trial of azacitidine with or without vorinostat in acute myeloid leukemia (AML) patients (NCT01617226). Prof. Craddock explains that it addressed the fundamentally question of how we can increase the clinical activity of azacitidine in older AML patients. Azacitidine represents an advance in the treatment of elderly AML patients, who are not eligible to undergo intensive chemotherapy. However, Prof. Craddock explains, the complete remission rates (CRR) are only in the region of 25% and all patients will ultimately relapse. Therefore, there is an urgent need to identify new strategies for these patients. There is evidence that adding a histone deacetylase inhibitor to azacitidine, amends its anti-leukemic activity. The RAvVA trial asked whether adding vorinostat augments the clinical activity of azacitidine in patients with high-risk AML and MDS. The primary endpoints were overall response rate (ORR) at 3 or 6 months and overall survival (OS). They also wanted to understand more about how these drugs work and the mechanism of relapse; therefore they quantitated leukemic stem progenitor cells. Although vorinostat was reasonably well-tolerated, it did not increase ORR and OS. According to Prof. Craddock, in a setting of AML, it is therefore probably not worth investing more effort into looking at combinations with histone deacetylase inhibitor, unless they have a significantly different mechanism of action in the next generation. He further explains that although they observed a substantial reduction in leukemic stem progenitors in patients achieving CR, azacitidine does not appear to eradicate this population. Recorded at the 2016 American Society of Hematology (ASH) Annual Meeting, held in San Diego, CA.