Safety, Efficacy of 3-day Administration Schedule of Consolidation Cytarabine in Adults With AML

Consolidation therapy with intermediate- to high-dose cytarabine is crucial in the prevention of acute myeloid leukemia relapse.¹ In this Q&A, Kendall Diebold, DNP, FNP-C, answers questions about her team’s research titled “Outcomes of 3- Versus 5-Day Administration Schedule of Consolidation Cytarabine in Adults with Acute Myeloid Leukemia." 

This Q&A is a transcription of a video interview. Watch the full video here. 

Consultant360: Please provide some background and an overview of your poster discussion at ASCO 2023 titled “Outcomes of 3- versus 5-day administration schedule of consolidation cytarabine in adults with acute myeloid leukemia.”

Kendall Diebold: My poster was an examination of three-day consolidation with high-dose cytarabine known as HDAC compared to five-day, and it was comparing essentially consolidation chemo that was given over three days versus the five days for convenience. I'll refer to the three-day cytarabine as AC123 and the five-day cytarabine as AC135. What we did was, traditionally we've always given HDAC 135. There's really no pharmacokinetic rationale for this, but that's kind of what we've always used, traditionally speaking. And that information initially arose from the CALGB study that was done in Europe. Since that time, there have been two additional studies also done in Europe that looked at three-day cytarabine, neither of which looked at age groups greater than 60 years of age. When COVID-19 hit, we started transitioning some of our patients over to AC123, kind of out of necessity to minimize hospitalizations, and to save up some hospital beds.

So our study included all patients with AML who had achieved the CR following their intensive induction chemotherapy and receiving consolidation treatment between January 1st, 2020, and December 31st, 2021. We then looked at data to determine the time to count recovery, specifically ANC recovery greater than 1000 per microliter, hemoglobin greater than eight, and platelets greater than 75,000 per microliter. All of our patients received GCSF on either day four or day six. Patients who received AC135 received inpatient consolidation, and those in 123 received outpatient. Both the GCSF and the inpatient/outpatient components were just performed per institutional protocol.

So essentially what our study found was that the AC123 group had a faster time to count recovery by about three to four days. Within the greater than aged 60 group, the count recovery was still quicker, it was about by two to three days rather than three to four, but it was still faster than in the AC135 group, overall. Our hospitalization rate was lower in the AC123 cohort. It was about 13% compared to about 29% in the AC135 group, and we didn't have any statistically significant differences in neutropenic fevers or bacteremia bleeding complications. But we did have overall lower rates, specifically with neutropenic fever. There was about a 5.5% rate of neutropenic fever in the AC123 group compared to closer to 15% in the AC135 group. And then our study also found that it was safe for the greater than 60 years of age group, that there weren't any additional safety triggers with them, and that they could safely receive that consolidation therapy as well.

C360: How do the results of this study impact clinical practice?

Kendall Diebold: I think that this is really good for clinical practice for several reasons. I think that it shows us that we have a safe and effective way of consolidating our older patients because I think that's kind of long term been a complicated issue of what can our greater than 60 patients really handle, especially when you consider their age, their overall performance status. I also think it's helpful in potentially moving more institutions across the nation to a 123-consolidation schedule, which can be done outpatient and requires not the hospital beds, fewer hospital resources, and then also with that faster time to count recovery, it's potentially freeing up some of the resources that we would normally use on transfusions. If their counts are recovered faster, then maybe we don't need to give them as much transfusion support. And then finally, that lower rate of neutropenic fevers, the lower rates of hospitalizations, which is also more time at home for our patients.

C360: What’s next for research on this topic?

Kendall Diebold: One of the things that we'd like to do is, so our data for overall survival and relapse-free survival rates are still being analyzed, but I think we'd like to finish that. I think we'd like to kind of look at this as it relates to post-transplants as well, specifically seeing what that overall survival, what that looks like when you add in. When you look at our AC123 cohort, there was a much higher grouping of poor-risk karyotypes in our AC123 groups, so they were a higher-risk group in general. And so I think looking at them and how their post-transplant mortality is and comparing that all is important specifically to our HDAC.

I also think that if we have the means to look at the actual amounts of blood transfusions and platelet transfusions that are required, that would be important just to kind of get some more firm numbers. That's challenging at our institution because so many of our patients are treated at tertiary centers in between cycles, but we did actually obtain a lot of the data from those centers, and so I'm hopeful that maybe we will be able to look at that as well.

The simplest take-home message is that our study demonstrates that AC123 as compared to AC135 is safe, and it leads to earlier hematopoietic recovery, both in adults over and under 60 years of age, and that we should consider it as an acceptable schedule of consolidation therapy. So that's kind of the simplest take-home message.

I think the other things that are important to remember are that there are fewer hospital complications, so fewer hospitalizations, a lower rate of neutropenic fevers, and then a faster time to count recovery. And then above all of that, I think anything that we can do to get our patients out of the hospital and at home with their families, I think that's a really good thing, and that's something that anything that we can do to help with that is a good thing.

C360: What are the overall take-home messages from this study and from our conversation today?

Kendall Diebold: I think that one of the things that we really wanted to make sure that our study showed was that we looked at that greater than 60 age group. So I think just to kind of give a little bit more background about that, those patients tended to do actually really well. Our total number, we had 90 patients in the total study for a total of 212 encounters. 71 of those encounters were in patients greater than 60 years of age. That correlates to about 32 patients. So about a third of our patients in total were greater than 60. They did really well. They had a 9.7% neutropenic fever rate, so still lower than that AC135 kind of group overall, and a 23% hospitalization rate. So again, it's still lower than when you're just looking at the AC135 group specifically. And then their count recovery was by about that two days that I mentioned. But the time to count recovery was statistically significant for both platelets and the ANC. And so I think that really just speaks volumes to having a safe method of consolidation for that specific group.

Reference:

1. Diebold K, Bachiashvili K, Hassan O, et al. Outcomes of 3- versus 5-day administration schedule of consolidation cytarabine in adults with acute myeloid leukemia. Talk presented at: 2023 ASCO Annual Meeting. June 2-6, 2023. Accessed June 19, 2023. https://meetings.asco.org/abstracts-presentations/220058

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