Less-Intensive Therapies Increase Mortality Risk, But Decrease Hospital Stay, in Older Patients With AML

Although the use of less-intensive therapies is associated with an increased risk of mortality in older patients with acute myeloid leukemia (AML), patients treated with these therapies also spend fewer days in the hospital, according to findings published in Blood.

Mohamed Sorror, MD, of Fred Hutchinson Cancer Research Center, who led the study, said the findings suggest clinicians routinely consider less-intensive therapies for older patients. Instead, older patients should be referred to academic AML centers that can provide clinical trials to further explore the role of intensive chemotherapy.

In their analysis, Dr. Sorror and colleagues retrospectively evaluated a cohort of 1,292 patients with AML who were treated at six collaborating tertiary centers. The study also included a prospective observational cohort of 692 patients with AML treated between 2013 and 2017 at 13 centers.

Investigators assessed quality of life (QOL), measures of function, and outcomes between patients who received less-intensive versus more-intensive AML therapies. In the prospective cohort, the therapies’ effects on Karnofsky performance status (KPS), QOL, and physicians’ perceptions of cure were assessed.

In the retrospective cohort, 293 patients received less-intensive therapies and 999 patients were treated with intensive therapies. The median age of these patients was 60 years old. Patients in the retrospective cohort who received less intensive therapies were older and had more comorbidities, more adverse cytogenetics, and worse KPS.

The investigators used an AML composite model (AML-CM), which assigned higher scores based on older age, higher comorbidity burden, and adverse cytogenetic risks. A total of three distinct prognostic group scores were identified, defined as scores 4 to 6; 7 to 9; and 10 or higher. (See TABLE).

In the retrospective population, less-intensive therapies were associated with a significantly higher likelihood of receiving allogeneic hematopoietic cell transplantation irrespective of whether they had AML-CM scores of 4 to 6 (hazard ratio [HR] = 0.40; 95% CI 0.22-0.72; p=0.002), 7 to 9 (HR=0.29; 95% CI 0.14-0.63; p=0.002), or 10 or higher (HR=0.29; 95% CI 0.13-0.65; p=0.003).

Additionally, less intensive therapies were significantly associated with higher mortality risks in the retrospective cohort, among patients with AML-CM scores of 4 to 6 (adjusted HR=1.82; 95% CI 1.25-2.63; p=0.002) or 7 to 9 (adjusted HR=1.67; 95% CI 1.22-2.27; p=0.002).

Among 191 patients ages 70 to 79 with known AML-CM scores of 4 or higher, the HR for mortality was significantly higher with less-intensive treatment (HR=1.38; 95% CI 1.00-1.90, p=0.05), the authors reported.

Approximately 21% of the prospective cohort received less-intensive regimens. A lower proportion of those who received less-intensive therapies ranked “cure” as more important than prolonged life or better QOL (69% vs 82%). Nearly half of patients (49%) who received less-intensive therapy ranked cure as more important than QOL, while 30% considered QOL more important than cure.

An analysis adjusted for additional age cutoffs, physician-assigned KPS, and clinicians’ perception of cure chances found no significant differences in mortality between the two therapeutic approaches within the prospective population.

However, an overall analysis found the use of less-intensive therapies was associated with less time spent in the hospital compared with intensive therapies within the first three months after starting treatment (16.6 vs. 37.4 days, respectively; p<0.0001).

“Older patients who are interested in achieving longer survival should have a discussion with their physicians about what clinical trials are currently available that explore the role of intensive chemotherapy in older patients,” Dr. Sorror concluded. “We believe our study is the first step of reevaluating the role of intensity of therapy in AML and older patients that eventually could lead to improvement in the overall outcomes.”

He added that the study highlights the importance of considering geriatric assessment for older patients with AML “to get a better sense of their overall health and not to rely on standard measures such as performance status scales or merely age.”

A primary limitation of this study was its observational nature, in addition to its lack of a randomized protocol and control.

To address the study’s inherent limitations, Dr. Sorror and colleagues are currently working to launch a multicenter, national randomized clinical trial to investigate whether the addition of intensive chemotherapy to targeted novel AML therapy could result in better outcomes compared with less-intensive therapies alone.

The authors report no relevant conflicts of interest.

Reference

Sorror ML, Storer BE, Fathi AT, et al. Multi-site 11-year experience of less-intensive versus intensive therapies in acute myeloid leukemia. [published online ahead of print, 2021 Apr 28]. Blood. doi: 10.1182/blood.2020008812.