Advancements in the management of medically less-fit and older adults with newly diagnosed acute myeloid leukemia

ABSTRACT

Introduction: Treating acute myeloid leukemia (AML) in older adults remains daunting. The unique biology often renders conventional chemotherapies less effective. Accurately predicting the toxicities of treatment is another unresolved challenge. Treatment planning thus requires a good knowledge of the current trial data and familiarity with clinical tools, including formal fitness and geriatric assessments. Both obstacles – disease biology and patient fitness – might be easier overcome with specific, AML cell-targeted agents rather than traditional cytotoxic chemotherapy. This may be the future of AML therapy, but it is not our current state.

Areas covered: Herein, the authors appraise the data supporting a standard induction approach, including an outline of how to predict treatment-related mortality and a review of the most up-to-date methods of geriatric assessment. They also discuss treatment expectations with less-intense therapies and highlight novel agents in development. Finally, they provide a basic approach to choosing treatment intensity.

Expert opinion: In an older and/or medically less-fit patient, treatment choice should begin with a thorough disease assessment, a formal evaluation of patient fitness and frailty. There should also be a clear communication with the patient and patient’s family about the risks and anticipated benefits of either an intense or nonintense treatment approach.

KEYWORDS:

• Acute myeloid leukemia (AML)
• geriatric assessment
• older adult
• resistance
• therapeutic fitness
• treatment
• treatment-related mortality

Declaration of interest

LC Michaelis is/has acted as a consultant to Incyte, TG Therapeutics, Novartis and Celgene. HD Klepin is a scientific consultant to Genentech and contributes to UpToDate. RB Walter has received laboratory research grants and/or clinical trial support from AbbVie, ADC Therapeutics, Amgen, Amphivena Therapeutics, Aptevo Therapeutics, AROG Pharmaceuticals, Celator/Jazz Pharmaceuticals, Covagen, Pharmacyclics, Seattle Genetics and Stemline Therapeutics. He also has ownership interests with Amphivena Therapeutics; and is (or has been) a consultant to Amphivena Therapeutics, BioLineRx, Covagen, Emergent Biosolutions (now Aptevo Therapeutics), Race Oncology, Pfizer Inc, Jazz Pharmaceuticals and Seattle Genetics. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Article highlights

• Many older patients are not treated despite data demonstrating both safety and efficacy even in patients in their eighth decade.

• Tools exist to predict the rates of morbidity and mortality with classical induction therapy.

• Novel studies on the use of geriatric assessments in hematologic malignancy patients can provide patient-centered predictions for toxicity of therapy as well as interventions that can be implemented during the cytopenic phase to prevent physical decline.

• Cytotoxic induction algorithms have changed with several newly approved drugs, including GO, CPX-351, and enasidenib.

• Novel approaches in clinical trials include the use of inhibitors of BCL2 and mutated IDH1 as well as antibody-based therapies. However, the latter will likely be more challenging in AML compared to ALL.

• The heterogeneity of the disease and of the population that develops it means that clinical trial in the future will need to be imaginative and nimble. It also underscores the importance of screening newly diagnosed patients for participation in these studies.

This box summarizes key points contained in the article.

Additional information

Funding

This manuscript has not been funded.