Multisite 11-year experience of less-intensive vs intensive therapies in acute myeloid leukemia

• Published in: Blood 2021-08, Vol.138 (5), p.387-400
• Main Authors: Sorror, Mohamed L., Storer, Barry E., Fathi, Amir T., Brunner, Andrew, Gerds, Aaron T., Sekeres, Mikkael A., Mukherjee, Sudipto, Medeiros, Bruno C., Wang, Eunice S., Vachhani, Pankit, Shami, Paul J., Peña, Esteban, Elsawy, Mahmoud, Adekola, Kehinde, Luger, Selina, Baer, Maria R., Rizzieri, David, Wildes, Tanya M., Koprivnikar, Jamie, Smith, Julie, Garrison, Mitchell, Kojouri, Kiarash, Leisenring, Wendy, Onstad, Lynn, Nyland, Jennifer E., Becker, Pamela S., McCune, Jeannine S., Lee, Stephanie J., Sandmaier, Brenda M., Appelbaum, Frederick R., Estey, Elihu H.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Critical Care; Disease-Free Survival; Female; Humans; Leukemia, Myeloid, Acute - mortality; Leukemia, Myeloid, Acute - therapy; Male; Middle Aged; Myeloid Neoplasia; Prospective Studies; Quality of Life; Retrospective Studies; Risk Factors; Survival Rate
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2020008812

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. •In 2 study cohorts, less-intensive therapies increased mortality in each of 3 risk groups defined by age, comorbidities, and cytogenetics.•The differences became nonsignificant after accounting for physician perception of cure, emphasizing the need for a randomized trial. [Display omitted]