Advances in treating acute myeloid leukemia (AML) have created new therapeutic opportunities for adult and pediatric patients. Our featured experts discuss the current state of practice in AML and where they think the field is heading next.

Over the past decade, we have seen a dramatic shift in the treatment of AML, with about a dozen new US Food and Drug Administration (FDA)–approved treatment options that include targeted therapies and small molecules. Venetoclax-based treatments have particularly improved outcomes for older patients who are unfit for intensive chemotherapy and whose treatment was previously palliative at best. These patients typically had a median survival of less than 12 months in clinical trials.

Beyond improvements in therapy, another advance is the opportunity to better stratify and personalize treatment for our patients. The recent long-term results from the VIALE-A study are a great example of both an advancement and an area with unmet needs. In this trial, older patients for whom intensive chemotherapy was inappropriate were randomized to receive venetoclax with azacitidine or azacitidine with placebo. At the final analysis, the median overall survival with venetoclax and azacitidine exceeded 1 year. Although we have improved outcomes, which is a clear win, the challenge is that this treatment strategy is not curative. So, we are trying to figure out how we can identify patients who will respond and optimize their treatment regimen to improve their outcomes further.

We previously focused on giving chemotherapy to patients with AML, but chemotherapy causes a lot of side effects. We have found leukemogenic mutations and understand the biology of AML better, which has led to the development of targeted agents. Many of these drugs are oral, and we hope that our patients will benefit from completely oral treatments at some point. An entirely oral regimen would be much easier to give a patient, as we could give them their pills and then see them less frequently. We cannot completely eliminate the need to monitor patients because they still have leukemia, and even the oral agents can suppress blood counts. Still, I think that a shift to oral agents would make life a lot easier for patients and practitioners.

We are making progress in treating older patients with AML by beginning to use targeted agents more effectively. I think that, in the future, we will apply that knowledge from older patients down the age gradient to younger patients, like we have done for patients with Philadelphia chromosome–positive acute lymphoblastic leukemia.

Now, clinicians who treat children are trying to reduce the dose of cytotoxic therapy and the need for transplantation, and using measurable residual disease assessment to look at treatment response can help with that. Even with lower-intensity therapy, we have to be clever about using our combinations, as the best time to treat leukemia is the first time. That concept should not be forgotten.

We have made incredible progress in treating pediatric AML, with some groups of children reaching an 80% survival rate. What really contributed to this progress, from my point of view, is not new drugs but rather supportive care, as well as identifying patients who are at high risk of relapse and offering transplants to them at that time.

Twenty years ago, I typically recommended a transplant to approximately 25% of patients who had a matched sibling donor. Now, most of the clinical trials in AML using the current risk classification will offer transplants to approximately 50% of patients in complete response and some more after relapse and salvage therapy. This fundamental change in treating pediatric AML was achieved by identifying risk groups and providing bone marrow transplants, not by targeting specific subtypes.

We have achieved progress, but we are still not satisfied with our results. When 50% of patients receive a transplant, it creates a major problem in terms of long-term complications and quality of life. Supportive care is of incredible importance, as a lot of children have long-term sequelae from AML treatment, particularly bone marrow transplants.

Now, we are looking to the older patient population for lessons. Can we reduce intensive therapy for certain groups of patients in favor of integrating newer compounds such as azacitidine, venetoclax, or menin inhibitors (for patients with KMT2A-mutated leukemia)? We probably have to separate genetically identified groups of patients and offer them more precision therapy.

I think that learning to integrate new compounds into frontline therapy will also be a major and important challenge as we move forward. The tendency has been to treat patients with the standard of care plus the compounds that we are interested in, so many times it is difficult to distinguish the efficacy and toxicity of one agent from that of others.