Acute Myeloid Leukemia: Evolving Through Targeted Therapies - Episode 18

Implications for Treating AML With CC-486

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Harry Paul Erba, MD, PhD: Gail, a couple of other things that came from the QUAZAR study that caught my attention. Unlike the last German study of 12 months of parenteral azacitidine, where those patients just got induction and then got maintenance or observation, in this study, 80% actually got consolidation. These were correctly treated patients with intensive chemotherapy. But I would also point out that in terms of that transplant option, the median survival was clearly better. But those survival curves, unfortunately, come right back together down around 2 to 4 years. It’s not a very good outcome. I personally wouldn’t replace transplant with this without a properly controlled study showing that.

My final point before I let you jump back in is that I’m really happy to hear you say that your patients tolerated it, because quality-of-life assessments make me a little anxious because I‘m not really a QoL [quality of life] kind of expert. I was worried about the grade 1 GI [gastrointestinal] toxicity, a few more infections, especially in older patients populations. But if you tell me your patients are tolerating it, and that’s New York, so they must be really tolerating it.

Gail J. Roboz, MD: A couple of things. First, I definitely agree with you that we are not prepared to say do this instead of transplant. But there are lots of nuggets of interesting things. For example, we know from Chris Hourigan’s data from EHA that if you’re an older patient and you’re going into a reduced-intensity allotransplant with MRD [minimal residual disease], that’s not going to go well. You’re not going to get cured of that. We have some data, both from this study and from others looking at azacitidine that might you be able to reverse MRD. Can you go from MRD positive to MRD negative? We are working on looking at those data.

If you have a patient in their late 60s who would be eligible only for reduced-intensity transplant, who has a significant proportion of MRD, for example, by next generation or by flow, you know that that patient’s outcome in transplant is not going to be what you want. Might you think about a maintenance approach in that patient? Again, these were questions that were not definitively answered by QUAZAR, but in putting together what we know about MRD, about the reduced-intensity transplant option versus a myeloablative transplant option for some of these older patients, it’s thought provoking.

From a quality-of-life perspective, we have to present the data exactly as they are. But let’s look into the nuances of it. First, the quality-of-life measures. We really worked hard on this. There were multiple significant tests. They were done throughout the entire follow-up period, which was long. What we saw on the GI [gastrointestinal] toxicity, it maybe took a couple of cycles for patients to straighten out. If you talk to my patient who’s been on it forever, she’ll tell you, “Oh, on those days, I might take an extra Pepto-Bismol, or I might not eat cheese on those days.” People work out what they need to do to manage the GI toxicity, and then it gets better. If you look at the cycles where it happens, it’s incredibly well managed.

Similarly, and this is not completely clear unless you dig into the weeds, but yes, there is some myelosuppression. But the significant myelosuppression occurred in the study at the time when patients were relapsing from their disease where the toxicities were because there was leukemia there, not so much because of the drug. So I actually was very, very encouraged and reassured that this is a feasible long-term ongoing therapy that doesn’t wreck people’s lives.

Harry Paul Erba, MD, PhD: Gail, those insights from an investigator on the trial are very important in considering maintenance where we know quality of life is going to be important for these older patients. There were a couple of follow-ups to QUAZAR. One of them was the quality-of-life data that Farhad Ravandi-Kashani presented. The second is that in the study, patients for whom the blast count started to go up between 5% and 15%, they went to a 21-day schedule from 14 days, and about 25% of those patients responded, and their survival looked to be better.

Gail J. Roboz, MD: Yeah, there were 3. Ravandi presented, so I presented the quality of life. That’s actually in a talk which is I believe available for eternity on video. Then Farhad did a poster on the patients over 75 years old.

Harry Paul Erba, MD, PhD: Yes, that’s the one.

Gail J. Roboz, MD: He did a great job. It’s 1 of these interactive posters that I found to be a fun aspect of the virtual meetings. Somehow, when you’re in a poster hall with 9000 people and bad beer, bagels, and stuff, you can’t focus as well as when the author is walking you through it. But he will walk you through that poster if you look at it on the EHA site. You can see that these are older patients. These are exactly the patients you would like not to do a transplant on, and they actually had a survival benefit, tolerated the drug, etc.

The third data set was regarding the salvage option of patients who had from 5% to 15% blasts who look like they were in early relapse, and actually by increasing from 14 to 21 days in those patients, we were able to get some of those patients back on track. That goes along with Uwe Platzbecker and some of the RELAZA2 data suggesting that staving off relapse is a potential concept of application of HMAs [hypomethylating agents]. They were not using CC-486. They were using regular azacitidine in that.

Harry Paul Erba, MD, PhD: The benefit in survival in the MRD-positive patient subgroup—there’s a lot here. I agree with you: This is going to become a new standard of care. Imagine that, maintenance in AML after all this time. Hints along the way, but you’ve shown it now.

Transcript Edited for Clarity