Treating Elderly Patients With AML: Evaluating a Patient Currently on Therapy

Karolina Faysman

Let’s say our patient—an 80-year-old female with AML and a TP53 mutation, ECOG 2 to 3, baseline dementia, receiving oral therapy at home with venetoclax and azacitidine—is presenting for evaluation, with the potential to achieve a complete remission in the non-transplant setting. What's next for this patient?

These patients are receiving oral therapy at home, so we may not see them as frequently, maybe only once a month or so. So how do we help them be their own advocates, particularly if you share the patient with another healthcare provider? We have seen frequently where patients have gone to their doctor in the community and then they come to us and say, “Well, my doctor told me that I've had enough of this therapy.” But so long as the patient tolerates therapy, there's no inappropriate AEs that the patient's unable to tolerate, and there's control of the disease—we have outcome—AML patients like this should remain on therapy or at least some form of therapy. They may not necessarily be dosed as frequently, maybe we extend the dosing, give them longer holidays, or switch them to another hypomethylating agent that decreases the number of visits they have to make to the clinic¹—it’s all based on the patient and their individual condition.

Miki Haraguni

One of my patients recently wanted to have intravenous therapy, versus oral oncolytics that he could take at home, because he wanted to come to clinic more frequently! We all think that patients would like to be on oral oncolytics, but sometimes they want to come to clinic just to be social, which is another good point about the elderly population of AML patients. When you encounter patients like this, we should also look into other supportive care options, like social services, support groups, etc.

Karolina Faysman

Yes, patient preference is important to factor in. But what if the patient goes into potential transplant evaluation? How do we continue treating them until that takes place? At this point we're now focusing on minimization of potential comorbidities, and frequently, some of the oral regimens would be the ones to choose because of the lower risk for toxicities. When we deal with intravenous chemotherapeutic agents, cytotoxic agents, their toxicity profile is usually much more substantial than it is when we're dealing with oral chemotherapy. These patients who have to be on some form of maintenance until we give them a transplant would definitely benefit from ongoing treatment.

Miki Haraguni

Frequently patients ask how long they will be on ongoing treatment. I had a patient who developed pancytopenia; we didn't think he could make it to transplant, but we put him on venetoclax, which got him into remission, and now he is going to transplant. But his counts have to somewhat recover a little bit more. So do we give him 2 to 3 weeks off the venetoclax before transplant? What would you do?

Karolina Faysman

Well, like we did with another patient recently who also had pancytopenia, we dose adjusted the venetoclax, but we still kept him on the regimen. You could also reduce down from a dual therapy to a single agent if the patient is on venetoclax and azacitidine or another hypomethylating agent, maybe switching them to one. But the focus in the transplant population is to keep them in remission because we know that when they fall out of remission, putting them back in remission is an absolute nightmare.

Miki Haraguni

Right, and when something works, you want to stick with it. It's like a car that is barely running: you don't want it to stop because you may not be able to start it again. That's how we see patients when you get them in remission you want to keep them in remission as long as they're tolerating the regimen and as long as the toxicity profile is manageable.

With the transplant, it becomes a bit of a different picture because there is a curative approach, which involves more aggressive treatment prior to transplant, compared with a non-transplant, maintenance approach, which may involve careful dose reduction if the patient is not tolerating therapy well and longer-term treatment, so there's a different focus. But even in the non-transplant patient population, you still want to produce as long of a remission as possible, regardless of the type of patient, like your patient with severe dementia or a fully functioning 86-year-old who runs his own farm. Again, the focus is all the same: to keep them in remission as long as possible with a manageable adverse event profile. And that’s why it’s so important for us as APPs to closely monitor these patients to catch any issues that come up.

Karolina Faysman

With these patients, as they get through more and more treatment cycles, we do usually see the pancytopenia improve because the disease burden is no longer there. We may be able to take them off of some of the antibacterial/antimicrobial agents. Their energy improves, although I know for a lot of patients, as they go further into treatment, even though their hemoglobin improves, fatigue continues and may increase. A lot of patients say that with the prolonged use of hypomethylating agents and/or targeted therapy, they develop more fatigue, so how do we help them manage the fatigue?

Miki Haraguni

We need to first assess their sleep patterns and their nutrition, and check on their hormones, including thyroid function and testosterone functioning in males. We also need to rule out infectious causes.

Karolina Faysman

Yes, all of those things have to be checked. I will also say that fatigue seems to be more of an issue in patients on long-term therapy. Pancytopenia and GI symptoms are under control usually, but the fatigue is something that we see more profoundly as therapy goes on. However, sometimes I wonder if patients have had fatigue all along, but now that they feel better otherwise, they're focusing more on the fatigue part.

Miki Haraguni

That’s a good point.

Karolina Faysman

And it's hard to quantify the fatigue. My fatigue level of 7 and your fatigue level of 7 are different. So I try to define it by connecting it to an activity. For example, if a patient tells me that their fatigue level is 7, I ask them what normal activity the fatigue is keeping them from doing? They might say, “Well, I like to walk my dog five blocks, but now I can only walk one block and then I'm done.” Then you can use that as your baseline to assess whether the fatigue is getting better or worse moving forward.

Miki Haraguni

I like that approach. We don't really want to dose adjust the drug if the fatigue really isn’t a big issue. We shouldn’t minimize a patient’s report of fatigue by any means, but we should try to quantify it as best as possible. This also helps ensure continuity of care, because any member of the healthcare team who sees this patient later on down the road can use that activity-focused baseline to measure changes in fatigue level.

Karolina Faysman

In the elderly patient population, other important factors in making therapy decisions are their geriatric assessment, which gives us insight on their functional ability, cognition and mental health, and even their socioenvironmental situation, as well as the fact that they may be on multiple other medications, so it’s important to check for any drug interactions. All of that will play a role in the management of a patient when we're dealing with oral oncolytic regimens. And even if they’re not taking oral oncolytics, they still go home at some point, and they're not under your care.

Miki Haraguni

Based on that assessment, we can determine if there's additional assistance needed for this patient, like a social worker. You and I come from an academic perspective, having a lot of both medical and non-medical support, but that definitely may be lacking for APPs in small community settings. Calling on outside support systems such as church and other social centers may be beneficial. Just like it takes a village to raise a child, it can take a village to get an elderly patient through AML treatment. As APPs, we need to help connect our patients with the resources and support they need.