In patients with acute myeloid leukemia (AML) in remission following intense treatment, measurable residual disease (MRD) predicted early recurrence and poor survival. Postremission maintenance treatment that maintains MRD negative or converts MRD+ patients to MRD status might postpone or avoid relapse and increase overall survival (OS). Oral azacitidine (oral-AZA; formerly CC-486), a hypomethylating agent, significantly prolonged OS and relapse-free survival (RFS) compared to placebo in patients aged 55 with AML in first remission after intensive chemotherapy who were not candidates for hematopoietic stem cell transplantation in phase 3 QUAZAR AML-001 trial. MRD (0.1% leukemic cells in bone marrow) was measured in this experiment using multiparameter flow cytometry in serial samples obtained at baseline and on day 1 of every three cycles. Baseline MRD status was highly linked with both OS and RFS, as predicted. 

In multivariate analyses, oral-AZA significantly improved OS and RFS compared to placebo, regardless of baseline MRD status. Oral-AZA therapy significantly increased the duration of MRD negativity by 6 months compared to placebo and resulted in a greater rate of conversion from MRD+ at baseline to MRD during treatment: 37% vs 19%, respectively. In the oral-AZA arm, 24% of MRD responders achieved MRD negative more than 6 months after starting therapy. Despite the fact that the presence or absence of MRD was a robust predictor of OS and RFS, there were additional survival advantages with oral-AZA maintenance medication compared to placebo, regardless of patients’ MRD status at baseline.

 

Reference:ashpublications.org/blood/article-abstract/139/14/2145/483370/Oral-azacitidine-prolongs-survival-of-patients?redirectedFrom=fulltext

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