KEY TAKEAWAYS
- Phase 3 QUAZAR AML-001 trial aims at prolonging OS and RFS among HSCT ineligible AML patients of advanced ages by providing maintenance therapy after their first remission post-IC.
- Patients were randomized and given either 300mg of Oral-AZA or a placebo in 28-day cycles.
- Oral-AZA patients showed longer survival rates at the primary cutoff date (July 2019) as well as on the updated cutoff date (March 2022) and higher conversion rates from MRD+ to MRD- during the therapy.
- Oral-AZA proved effective, feasible, and tolerable as a long-term maintenance therapy.
The Phase 3 QUAZAR AML-001 trial was a randomized, double-blind study to identify the safety and efficacy of Oral Azacitidine (Oral-AZA), using placebo as control, in patients with Acute Myeloid Leukemia (AML) who may be ineligible for Hematopoietic Stem Cell Transplantation (HSCT). This study aimed at prolonging the Overall Survival (OS) of the HSCT-ineligible patients in complete remission. March 2022 was the cutoff for the updated OS outcomes, with the median follow-up time at 55.5 months.
472 patients of ≥55 years (median age=68 years) who were diagnosed with intermediate-or poor-risk cytogenetics were randomized into 2 groups. The patients had already achieved either their first Complete Remission (CR) or CR with incomplete blood count recovery (CRi) with IC. One of the groups (n=238) received 300mg of Oral-AZA per day, while the other (n=234) received a placebo for 14 days in 28-day repeated cycles. After the unblinding of the trial, patients in the Oral-AZA group had the option to continue their treatments.
The updated data from March 2022 showed that 25 patients were still undergoing Oral-AZA maintenance. 54 patients received ≥36 treatment cycles, while 34 received ≥60. The estimated 3-year survival rate in Oral-AZA was 37.4%, while that of placebo was 27.9%. This showed a 9.5% increase with Oral-AZA [95%CI +0.9% to +18.1%]. Similarly, there was a 6.3% increase in the 5-year survival rates from 20.1% to 26.5%.
The median OS was estimated by Kaplan–Meier methods and compared using stratified log-rank tests. They remained unchanged from the primary cutoff date (July 2019; median follow-up 41.2 months) with 24.7 months for Oral-AZA versus 14.8 months for placebo.
Post-IC MRD (measurable residual disease) was also assessed at screening using multiparameter flow cytometry. It found that 47% of patients were MRD+. The survival rates in the placebo group were significantly influenced by the MRD- status of the patients, however, it bore no significance in the Oral-AZA group. Additionally, a higher conversion rate from MRD+ to MRD- was seen in the Oral-AZA group by mitigating the post-IC MRD+. Thus, MRD- status was important for long-term survival in both groups.
The updated data support the feasibility and tolerability of Oral-AZA as long-term maintenance therapy for AML patients in first remission after chemotherapy, ineligible for HSCT, to prolong the OS and RFS (relapse-free survival).
Source: https://onlinelibrary.wiley.com/doi/10.1002/ajh.26847
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT01757535
Wei, A. H., Döhner, H., Sayar, H., Ravandi, F., Montesinos, P., Dombret, H., Selleslag, D., Porkka, K., Jang, J. H., Skikne, B., Beach, C. L., Prebet, T., Zhang, G., Risueño, A., Ugidos, M., See, W. L., Menezes, D., & Roboz, G. J. (2023). Long-term survival with oral azacitidine for patients with acute myeloid leukemia in first remission after chemotherapy: updated results from the randomized, placebo-controlled, phase 3 QUAZAR AML-001 trial. American journal of hematology, 10.1002/ajh.26847. Advance online publication. https://doi.org/10.1002/ajh.26847
