Oral azacitidine prolongs survival of patients with AML in remission independent of measurable residual disease status
- Author(s)
- Roboz, GJ; Ravandi, F; Wei, AH; Dombret, H; Thol, F; Voso, MT; Schuh, AC; Porkka, K; La Torre, I; Skikne, BS; Zhong, J; Beach, CL; Risueño, A; Lopes de Menezes, D; Ossenkoppele, GJ; Döhner, H;
- Journal Title
- Blood
- Abstract
- Measurable residual disease (MRD) in patients with acute myeloid leukemia (AML) in remission after intensive chemotherapy is predictive of early relapse and poor survival. Post-remission maintenance therapy that prolongs MRD negativity or converts MRD positive (MRD+) patients to MRD negative (MRD-) status may delay or prevent relapse and improve overall survival (OS). In the phase 3 QUAZAR AML-001 trial, oral azacitidine (Oral-AZA; formerly CC-486), a hypomethylating agent, significantly prolonged OS and relapse-free survival (RFS) compared with placebo in patients aged ≥55 years with AML in first remission after intensive chemotherapy who were not candidates for hematopoietic stem cell transplantation. In this trial, MRD (≥0.1% leukemic cells in bone marrow) was assessed by multiparameter flow cytometry in serial samples collected at baseline and on day 1 of every 3 cycles. As expected, baseline MRD status was significantly associated with both OS and RFS. Multivariate analyses showed Oral-AZA significantly improved OS and RFS vs. placebo independent of baseline MRD status. Oral-AZA treatment also extended the duration of MRD negativity by 6 months vs. placebo, and resulted in a higher 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 negativity >6 months after treatment initiation. While presence or absence of MRD was a strong prognostic indicator of OS and RFS, there were added survival benefits with Oral-AZA maintenance therapy compared with placebo, independent of patients' MRD status at baseline. NCT01757535 Clinicaltrials.gov.
- Research Division(s)
- Blood Cells And Blood Cancer
- PubMed ID
- 34995344
- Publisher's Version
- https://doi.org/10.1182/blood.2021013404
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- Refer to copyright notice on published article.
Creation Date: 2022-02-18 11:34:04
Last Modified: 2022-02-18 02:30:27