Dr. Stein on Real-World Data, Targeted Combinations, and Immunotherapy in AML

Eytan M. Stein, MD, explains why real-world data matters in acute myeloid leukemia (AML). He also discusses how combining targeted agents could drive the next wave of progress, and why immunotherapy has yet to succeed in myeloid disease the way it has in multiple myeloma and lymphoma.

Stein, a hematologist/oncologist at Memorial Sloan Kettering Cancer Center, begins with the limits of clinical trial data. Trials have strict entry criteria and often exclude patients with abnormal kidney, liver, or cardiac function. As a result, trial results reflect a selected population that may be healthier than patients treated in routine practice. They need to be interpreted in light of who was actually enrolled.

Real-world data, which is often retrospective, looks at what happens to patients treated outside of trials who may not have met every eligibility criterion. According to Stein, these analyses show how a drug may perform once it is used in a broader population.

He also points to racial disparities as a key reason this evidence matters. In the United States, underrepresented minorities are under-enrolled in many clinical trials, and real-world analyses help show how therapies work in those populations. Taken together, retrospective data can confirm primary trial findings. It can also give physicians confidence that a drug will work not only for a relatively fit clinical-trial patient, but for patients who may not be as healthy.

Turning to treatment, Stein highlights the targeted agents developed over the past 10 to 15 years. He identifies combination strategies as the area where significant advances are likely. Targeted agents now exist for IDH, FLT3, and NPM1 mutations, yet some patients with newly diagnosed AML carry all 3. That raises open questions. Should these patients receive chemotherapy with 3 targeted agents or with 1, and which targeted agent is best? Stein asks whether AML will follow the path of multiple myeloma, where combining many drugs has become a way to cure patients or bring them to a curative transplant, or whether a different approach will emerge.

Stein also addresses immunotherapy in AML, an area where he says there has not yet been substantial progress. Bone marrow transplant is itself a form of immunologic therapy, but apart from transplant, immune-based treatments have not been successful in AML. This contrasts with multiple myeloma and lymphoma, and he notes how much survival has improved in multiple myeloma over the past 15 years. He emphasizes the need to understand why immunotherapies are not working in myeloid leukemia, so that approaches can be developed to make them successful.