Discussing Rationale of Azacitidine Plus Maintenance Therapy in AML

Naval Daver, MD associate professor, Department of Leukemia, MD Anderson Cancer Center, explains the rationale for the phase II QUAZAR trial, which assessed the efficacy and safety of azacitidine (Vidaza) in patients with acute myeloid leukemia (AML).

The phase II trial of azacitidine with supportive maintenance therapy in patients with AML was designed based on immune profiling performed at MD Anderson Cancer Center. About 6 years ago, the profiles showed that newly diagnosed patients with AML and patients with relapsed AML had PD-1 expression. About 30% to 40% of these patients had high PD-1 expression on their T cells.

The degree of PD-1 expression on the T cells also increased in patients with relapsed disease. This increase was expected because these cells become exhausted after subsequent relapses and the tumor microenvironment becomes more immunosuppressive.

Based on this background knowledge, the investigators of QUAZAR trial hypothesized that introducing a PD-1 inhibitor in the relapsed setting of AML could potentially reverse the T-cell exhaustion and improve response rates.