Allogeneic Transplantation in Elderly AML Patients

In acute myeloid leukemia (AML) patients aged 60 years or older, allogeneic stem cell transplantation (AlloSCT) enhanced clinical outcomes during first complete remission (CR1), according to results of an abstract presented by Raynier Devillier, MD and colleagues at the American Society of Hematology (ASH) 2018 Annual Meeting & Exposition, held December 1–4 in San Diego.

Patients aged 60 or younger with intermediate or unfavorable European Leukemia Net (ELN)-2010 risk are routinely considered for AlloSCT, which is curative. Secondary to concerns about heightened toxicity, however, this approach in patients aged 60-plus is contentious-especially in those with intermediate ELN risk.

In the current French multicenter study, Devillier and co-authors examined whether AlloSCT was beneficial in AML patients aged 60 years or older. Inclusion criteria were, age between 60 and 70 years and diagnosed with AML between 2007 and 2017, CR1 following intensive chemotherapy, and ELN-2010 intermediate or unfavorable risk groups. In total, 521 patients met inclusion criteria (median age 65 years; ELN intermediate risk group, 72%; ELN unfavorable risk group, 28%). In sum, 38% of patients (n=199) received transplant.

The investigators evaluated AlloSCT as a time dependent variable in survival calculations and employed a multivariate Cox model controlling for age, ELN group, and transplantation period, and stratified by transplantation center. They also utilized a multistate model.

Based on the results from the multistate model, the investigators found that 5 years post-CR1, few patients without AlloSCT survived, despite ELN risk group. Additionally, patients who were administered AlloSCT had a lower chance of relapse at 5 years (ELN intermediate risk group, 22%; ELN unfavorable risk group, 33%) vs patients who were not administered AlloSCT (ELN intermediate risk group, 68%; ELN unfavorable risk group, 78%).

“AlloSCT for CR1 AML patients over 60 years of age is routinely feasible and significantly improves outcome in both intermediate and unfavorable ELN-2010 risk groups,” concluded the authors. “Less than 10% of patients are long-term disease-free survival without AlloSCT, even in [the] intermediate risk group, supporting that AlloSCT remains the first curative option for these patients.“

In an interview with Cancer Network, Aaron T. Gerds, MD, MS, assistant professor of medicine in the hematology and medical oncology department at the Cleveland Clinic Taussig Cancer Institute, reflected on the findings of the current study.

“For the majority of patients who are diagnosed with AML, allogenic transplantation (allo-HCT) is the only therapeutic modality that has demonstrated curative potential. In order to minimize transplant-related toxicity in older or frail patients, the conditioning regimen intensity is often reduced,” he said. “However, this is at the cost of increased relapse as demonstrated by the BMT-CTN 0901 study.  It is possible with these trade-offs that allo-HCT, even though potentially curative, may not improve survival in older patients with AML. With prospective data to answer this question, several retrospective studies have been done. In abstract 209 [Devillier et al study], the authors used a multistate model that showed the outcomes for older AML patients are better with allo-HCT, in the setting of both intermediate and high-risk disease. It is a stark reminder of how aggressive this disease is, as less than 10% of patients had long-term disease-free survival without allo-HCT. This is further confirmation that patients with intermediate and high-risk AML in first remission should be referred for transplantation, irrespective of age.”