Assessing the Use of Oral Azacitidine in Acute Myeloid Leukemia Treatment


Experts discuss the pros and cons of using oral azacytidine to treat patients with acute myeloid leukemia.

Pharmacists on the oncology care team are poised to decide where and when to use the high-cost and high-value therapies currently available in the treatment of acute myeloid leukemia (AML), explained Bernard Marini, PharmD, BCOP, during a 2022 ATOPP panel discussion.

To demonstrate the considerations available for pharmacists in this decision, Marini started by providing a patient case.

“We're going to start with AP, who is a 68-year-old man who was diagnosed with AML, started on remission induction therapy with 7+3, and achieves CR1,” Marini said. “Of note, he is a normal male karyotype and his myeloid next-generation sequencing displays no mutations of interest.”

After completing induction chemotherapy, AP is given 4 cycles of HiDAC consolidation due to the lack of a suitable donor, which means he is unable to go on a stem cell transplant. For AP, the question becomes whether the patient should be administered maintenance therapy because of his inability to complete curative stem cell transplant, explained Marini.

Panel participant Lydia Benitez, PharmD, BCOP, explained that her response to this question would be no.

“I think we can all agree that we've seen numerous new, exciting therapeutics enter the market in the last 7 or so years, so it's a lot harder for my residents than it was for me,” Benitez said. “They have to learn a lot more primary literature. I think with that, they also have to learn how to actually interpret primary literature, so their evidence-based medicine skills from pharmacy school are very valuable.”

However, Benitez noted that, in order for patients to be cured of AML, it is still necessary to rely on intensive therapy followed by consolidation therapy, if the patient is high-risk or intermediate-risk, followed by allogeneic stem cell transplant.

“That is still our current option as newer agents usually have pretty short durations from response and they are not mature enough. As such, there definitely is a need for some type of therapy that can be given to patients that are unable to complete curative-intent therapy in order to extend their duration of life,” Benitez said.

Due to this need for noncurative therapy options, the National Comprehensive Cancer Network just added some recommendations based on the literature to address only those patients that have intermediate or higher disease, Benitez explained. For these patients, they are given intensive therapy with a goal of cure, but do not proceed with full intent consolidation.

However, Benitez noted that the idea of maintenance therapy is not new in the treatment of AML. There are a variety of trials that have been published over the past 10 years that look at the use of hypomethylating agents for patients who are in remission to try and extend that remission.

“The study that I would like to highlight is HOVON-97. I would like to highlight this study because it is a phase 3 trial of patients with AML or high risk MDS, greater than 60-years-old in first remission, after 2 or more intensive cycles of chemotherapy, and these patients were randomized to oral azacitidine for 5 days every 4 weeks for observation,” Benitez said. “What the study showed was that, in fact, giving maintenance therapy does improve disease-free survival. However, that disease free-survival benefit does not translate to differences in overall survival (OS).”

When prescribing oral azacitidine for a patient, Benitez noted that it is important to remain aware of the common adverse effects (AEs) of treatment that patients can experience as well. For azacytidine, the most common AE is nausea and vomiting, and in fact, most pre-medicated patients should be given antibiotics for the first few cycles.

“I would also like you to know that this agent is very costly. It is about $20,000 per month for patients,” Benitez said. “Finally, I want you to know that you should never think of this agent as equivalent to intravenous or subcutaneous azacitidine. In fact, this agent has very poor bioavailability.”

The data that got oral azacitidine approved were based on the QUAZAR AML-001 study, which was a phase 3 trial that investigated the treatment in adults with AML in first remission after induction plus or minus consolidation who were ineligible for allogeneic stem cell transplant. The primary endpoint of the study was OS, with secondary endpoints including survival and quality of life.

The investigators randomized patients into oral azacitidine or placebo arms, and then did 3-month assessments. If patients were in a CR, they could continue treatment. If they had some level of residual disease—5% to 15% was poor progression—they could either continue treatment or discontinue treatment. If they had more than 50% blast at any assessment, they would stop treatment.

“When we look at [OS] by number of consolidations—so remember, the majority of patients receive 0 to 1 consolidation—what is very clear is that the more consolidations you have, the less of a benefit oral azacitidine has,” Benitez said. “So patients that receive at least 1 consolidation, the hazard ratio was not statistically significant, and for patients who received 2 or more consolidations, there was also no significant difference. So, the takeaway message here is that the more consolidations a patient receives, the less of a benefit.”


Marini B, Benitez L, Rausch C. VEN-ting About Novel Therapies in Acute Myeloid Leukemia (AML). San Diego, CA: 2022 ATOPP Summit; July 15, 2022.

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