Less-intensive induction therapies are increasingly used in older patients with acute myeloid leukemia, assuming they are better than intensive induction. Using an AML-composite model (AML-CM) that assigns higher scores to older age, increased comorbidity-burdens and adverse cytogenetic-risks, we defined three distinct prognostic groups, and within each, compared outcomes after less-intensive versus intensive induction therapies in a multicenter retrospective cohort (n=1292) treated at six institutions from 2008-2012 and a prospective cohort (n=695) treated at thirteen institutions from 2013-2017. Prospective study included impacts of Karnofsky performance status (KPS), quality of life (QOL), and physicians' perceptions of cure. In the retrospective cohort, recipients of less-intensive therapies were older, had more comorbidities, more adverse cytogenetics, and worse KPS. Less-intensive therapies were associated with higher risks for mortality in AML-CM scores of 4-6, 7-9, and ≥10. Results were independent from receipt of allogeneic transplants and similar in those aged 70-79 years old. In the Prospective cohort, the two groups were similar in baseline QOL, geriatric assessment, and patients' outcome preferences. Higher mortality risks were seen after less-intensive therapies. However, in models adjusted for age, physician-assigned KPS and chances of cure, mortality risks and QOL were similar. Less-intensive recipients had lessened length of hospitalization (LOH). Our studies question the survival or QOL, except LOH, benefits from less-intensive therapies in patients with AML, including those aged 70-79 years or with high comorbidity-burden. A randomized trial in older/medically infirm patients is needed to better assess the value of less-intensive, intensive, or a combination of both therapies. ClinicalTrials.gov #NCT01929408.
Mohamed Lotfy Sorror, Barry E Storer, Amir T Fathi, Andrew M Brunner, Aaron T Gerds, Mikkael A Sekeres, Sudipto Mukherjee, Bruno C Medeiros, Eunice S Wang, Pankit Vachhani, Paul J Shami, Esteban Peña, Mahmoud Elsaway, Kehinde U A Adekola, Selina Luger, Maria R Baer, David Rizzieri, Tanya Wildes, Jamie Koprivnikar, Julie Smith, Mitchell Garrison, Kiarash Kojouri, Wendy M Leisenring, Lynn Onstad, Jennifer E Nyland, Pamela S Becker, Jeannine S McCune, Stephanie J Lee, Brenda M Sandmaier, Frederick Appelbaum, Elihu H Estey