Multisite 11-year experience of less-intensive vs intensive therapies in acute myeloid leukemia
Mohamed L. 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 Elsawy, Kehinde Adekola, Selina M. Luger, Maria R. Baer, David A. Rizzieri, Tanya M. 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 R. Appelbaum, Elihu H. Estey
Abstract
Less-intensive induction therapies are increasingly used in older patients with acute myeloid leukemia (AML). Using an AML composite model (AML-CM) assigning higher scores to older age, increased comorbidity burdens, and adverse cytogenetic risks, we defined 3 distinct prognostic groups and compared outcomes after less-intensive vs intensive induction therapies in a multicenter retrospective cohort (n = 1292) treated at 6 institutions from 2008 to 2012 and a prospective cohort (n = 695) treated at 13 institutions from 2013 to 2017. Prospective study included impacts of Karnofsky performance status (KPS), quality of life (QOL), and physician perception of cure. In the retrospective cohort, recipients of less-intensive therapies were older and had more comorbidities, more adverse cytogenetics, and worse KPS. Less-intensive therapies were associated with higher risks of mortality in AML-CM scores of 4 to 6, 7 to 9, and ≥10. Results were independent of allogeneic transplantation and similar in those age 70 to 79 years. In the prospective cohort, the 2 groups were similar in baseline QOL, geriatric assessment, and patient outcome preferences. Higher mortality risks were seen after less-intensive therapies. However, in models adjusted for age, physician-assigned KPS, and chance of cure, mortality risks and QOL were similar. Less-intensive therapy recipients had shorter length of hospitalization (LOH). Our study questions the survival and QOL benefits (except LOH) of less-intensive therapies in patients with AML, including those age 70 to 79 years or with high comorbidity burdens. A randomized trial in older/medically infirm patients is required to better assess the value of less-intensive and intensive therapies or their combination. This trial was registered at www.clinicaltrials.gov as #NCT01929408.