Treatment Options Expand for Older and Elderly Patients With AML

Pinkal Desai, MD

Pinkal Desai, MD

Several new agents have been approved by the FDA for the treatment of patients with acute myeloid leukemia (AML) over the last few years, offering patients more options than before. These include chemotherapy-based treatments, targeted therapies, and combinations of hypomethylating agents (HMAs).

Previously, physicians would treat AML with a 7+3 regimen. With so many treatments available today, physicians have to consider a number of factors to select which treatment is right for each individual patient. These factors include age, comorbidities, molecular profile, and patient preference.

In AML, elderly patients can fall into another category of patients, which are under the age of 75 years, and may be candidates for transplant or chemotherapy, and the elderly, which are not eligible for such aggressive treatment. The comorbidities are also important to consider in the older patients with AML because they will impact which treatments are more suitable for each patient.

It is also important to look at the molecular profile of the disease to select the right treatment. For example, patients with aFLT3mutation can be treated with a FLT3 inhibitor. Patients could also present with an IDH mutation, which could be treated with different therapies based on the way the disease presents.

Last, patient preference is important to consider when making these decisions. The patient can tell their physician whether or not they want to go to transplant and if they would prefer intravenous (IV) treatment or oral agents.

In an interview withTargeted Oncology, Pinkal Desai, MD, assistant professor of medicine at Weill Cornell Medical College, discussed the latest advancements in the treatment landscape for patients with AML, particularly for the older population. She also highlighted emerging treatment options that undergoing investigation now in clinical trials.

TARGETED ONCOLOGY: What are the current treatment options for older patients with AML?

Desai:Various options are available right now for the treatment of older patients with AML. From 2017 up until now, there have been about 7 drug approvals in AML. In the old days, we used to give 7+3 for patients who were young, and we would give HMAs for older patients. There was nothing more than that, but now we have all of these drug approvals for the frontline indication.

Some of the indications include targeted therapies, chemotherapy-based treatments, or combinations of HMAs with targeted therapy. This is a new world, and choosing which treatment is best for the patient depending on their molecular profile, the ultimate aim and goal of treatment has become a challenge. Treating leukemia has become much more difficult than it used to be. For practicing physicians, this is an important decision, and leukemia doctors spend hours thinking about what would be best first bite off the apple.

TARGETED ONCOLOGY: What types of factors go into the treatment decision for these patients?

Desai:The first thing that is important whenever a patient walks into the clinic is age. Even within the older population, there are going to be patients that are young enough to get chemotherapy, for example, and some people who are okay, but there is a lot of comorbidities, and maybe they do not tolerate chemotherapy. Patients over 75 years of age are not candidates for any chemotherapy.

The next thing to look at is the comorbidities because the older and elderly patients are 2 different populations. Getting into the comorbidities, such as heart function and kidney function, all of these things that are considered in the decision-making process. The other important aspect of leukemia management is the molecular profile of the leukemia. We have to sequence their leukemia, figure out what is the signature of that patient’s leukemia, whether they have aFLT3mutation or an IDHmutation. All of that goes into deciding what treatment [is best].

Also, another very important aspect is patient preference. There are patients who will indicate what they are willing to do and not do or if [they have] intent to transplant or not. These are all decisions that have to be taken into account before we say this would be the best induction strategy for that patient.

TARGETED ONCOLOGY: Could you discuss the recent approvals we have seen for the treatment of AML?

Desai:Going from the beginning, we have the approval of midostaurin, which is aFLT3inhibitor for younger patients with AML under 60 years, although the label is for everybody with a FLT3mutation. We have CPX 351, liposomal doxorubicin, and cytarabine, a fixed-dose, which is specifically a chemotherapy approved for secondary or therapy-related AML. We also have the targeted agents, which are ivosidenib (Tibsovo) and azacitidine (Vidaza), the IDH1/2 inhibitors that are approved for the frontline treatment. We have the BCL2 inhibitor venetoclax (Venclexta) that was approved in older patients over the age of 75 with AML or younger patients that cannot handle chemotherapy. That has been approved in combination with both HMAs and low-dose cytarabine. We also have approval with low-dose cytarabine in older patients along with glasdegib (Daurismo), which is a Hedgehog inhibitor.

We have all of these approvals now in frontline AML, and we have to decide which one to use.

TARGETED ONCOLOGY: What emerging agents are you looking forward to in AML?

Desai:Other novel FLT3 agents are currently being looked at. We have quizartinib in the frontline setting, and we are awaiting the data. There are other FLT3 inhibitors like crenolanib is also being looked at. This is mostly for younger patients, but they are novel FLT3 inhibitors that are currently being tested against midostaurin, which is currently considered the standard of care forFLT3-mutated AML.

In terms of the frontline setting, those are the most recent indications, but if you go beyond that, we also have been awaiting the final results of oral azacitidine as a maintenance treatment in AML, which is pretty huge and would be a big breakthrough depending on the data.

TARGETED ONCOLOGY: What challenges still remain in treating these older patients with AML?

Desai:The biggest challenge is still curing patients with AML. We are fortunate in this year of novel agents that we are increasing the number of patients who can go into remission, including older patients, particularly over the age of 70, that have never dealt with complete remission rates in the 70% range that we now get, which is very exciting.

In people who are younger and still eligible for transplant in the older category, whether these agents will impact overall survival and cure these patients is something we have yet to see and discover. Ultimately to a patient with AML, that is what matters; they want to be cured.

In older patients where we cannot transplant, how long can we keep them in remission with these novel agents? [Should we treat with a drug] either continuously or 1 after the other? Ultimately, it is the survival and curability of leukemia that we care most about. Getting a high remission rate is the first step toward it. Now we need to use all of these agents in combinations and as maintenance strategies to do more things post-transplant. There are several areas that can impact survival and curability of patients.

TARGETED ONCOLOGY: What other areas of research need to be addressed?

Desai:When you have somebody with multiple mutations that are targeted, for example aFLT3and IDHmutation, 5 different drugs could be given to the patient in the frontline, so selecting which agent is a very difficult challenge. You have to think hard about everything. Are we trying to transplant the patient? What is the patient preference in terms of the therapies? Do they prefer an oral regimen versus an IV regimen? What is the patient’s goal in the leukemia treatment? All of that goes into our decision making.