A uniquely patient-focused take on treating AML in older adults

Q: What about older adults with AML considered appropriate for antileukemic therapy but not for intensive antileukemic therapy?

Dr. Sekeres: This again gets to the question of what are a patient’s goals. It takes a very involved conversation with patients at the time of their AML diagnosis to determine whether they would want to pursue an aggressive approach or a less-aggressive approach. If a patients want a less-aggressive approach, and want nothing to do with a hospital stay, then they are also prioritizing initial quality of life. In this recommendation, based on existing studies, we didn’t have a preference for which of the available less-aggressive chemotherapies a person selects.

There’s also debate about what to do in those considered appropriate for antileukemic therapy, such as hypomethylating agents (azacitidine and decitabine) or low-dose cytarabine, but not for intensive antileukemic therapy. What did the available evidence seem to indicate about this issue?

There has been a lot of studies trying to add two drugs together to see if those do better than one drug alone in patients who are older and who choose less-intensive therapy. The majority of those studies have shown no advantage to getting two drugs over one drug.

Our recommendation is that in these situations a patient gets one drug, not two, but there are a couple of caveats. One caveat is that there has been a small study showing the effectiveness of one of those low-dose chemotherapies combined with the drug glasdegib. The second caveat is that there have been results presented combining one of these low-dose chemotherapies with the drug venetoclax. One of those was a negative study, and another was a positive study showing a survival advantage to the combination vs. the low-dose therapy alone. We had to couch our recommendation a little bit because we knew this other study had been presented at a conference, but it hadn’t come out in final form yet. It did recently, however, and we will now revisit this recommendation.

The other complicated aspect to this is that we weren’t 100% convinced that the combination of venetoclax with one of these lower-dose therapies is truly less-intensive therapy. We think it is starting to creep up toward more-intensive chemotherapy, even though it is commonly given to patients in the outpatient setting. It gets into the very complicated area of what are we defining as more-intensive therapy and less-intensive therapy.

Q: Is there a recommended strategy for older adults with AML who achieve a response after receiving less-intensive therapy?

Dr. Sekeres: This is also challenging because there are no randomized studies in which patients received less-intensive therapy for a finite period of time vs. receiving those therapies ad infinitum. Given the lack of data and also given a lot of anecdotal data out there about patients who stopped a certain therapy and relapsed thereafter, we recommended that patients continue the less-intensive therapy ad infinitum. So as long as they are receiving a response to that therapy, they continue on the drug.

Q: Of course, there are also unique considerations faced by older patients who are no longer receiving antileukemic therapy and have moved on to receiving end-of-life care or hospice care. What advice do the guidelines offer in this situation?

Dr. Sekeres: There are a lot of aspects of these recommendations that I think are special. The first is the focus on patient goals of care at every point in these guidelines. The second is that the guidelines follow the real disease course and a real conversation that doctors and patients have at every step of the way to help guide the decisions that have to be made in real time.