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Allogeneic HSCT appears safe, effective for older patients with AML
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Allogeneic hematopoietic stem cell transplantation may serve as preferred treatment approach for patients aged 60 years or older with intermediate- or adverse-risk acute myeloid leukemia in first remission, according to the results of a time-dependent analysis of four trials.
The median age for AML diagnosis is approximately 70 years. Although approximately 50% to 60% of patients enter first complete remission upon intensive induction chemotherapy, the risk for relapse remains high and overall outcomes remain discouraging.
Jan J. Cornelissen
“Effective post-remission therapy in elderly patients is desperately needed,” Jan J. Cornelissen, MD, PhD, of the department of hematology at Erasmus University Center Cancer Institute in Rotterdam, Netherlands, and colleagues from the HOVON and SAKK Leukemia Groups wrote. “Post-remission therapy can include continued chemotherapy, autologous hematopoietic stem cell transplantation (HSCT) or allogeneic HSCT, although maintenance treatment has never proven to be effective.”
Cornelissen and colleagues sought to assess the comparative value of allogeneic HSCT and other approaches — including no post-remission therapy — in patients with AML aged 60 years or older.
They conducted a time-dependent analysis using the results of four successive prospective AML trials conducted by the HOVON–SAKK Leukemia Groups. The studies — conducted between May 2001 and February 2010 — included data from 1,155 patients, of whom 640 achieved first complete remission following induction chemotherapy.
Post-remission therapy approaches included allogeneic HSCT following reduced-intensity conditioning (n = 97), gemtuzumab ozogamicin (Mylotarg, Pfizer; n = 110), chemotherapy (n = 44), autologous HSCT (n = 23) or no further treatment (n = 366).
Reduced-intensity conditioning regimens used by patients undergoing allogeneic HSCT included fludarabine (Fludara, Bayer HealthCare) combined with 2 Gy of total body irradiation (n = 71), fludarabine with busulfan (Busulfex, Otsuka Pharmaceutical; n = 10) or other regimens (n = 16).
OS at 5 years for all treatment groups — analyzed by a time-dependent analysis — served as the primary endpoint.
Thirty-five percent (95% CI, 25-44) of patients who underwent allogeneic HSCT achieved 5-year OS, compared with 21% (95% CI, 17-26) of patients who underwent no additional treatment and 26% (95% CI, 19-33) of patients who underwent additional chemotherapy or autologous HSCT.
The researchers observed that the European LeukemiaNET AML risk score appeared associated with OS at 5 years. A greater proportion of patients in the favorable-risk group (n = 65) achieved 5-year OS (56%; 95% CI, 43-67) than patients with intermediate-risk (n = 131; 23%; 95% CI, 19-27) or adverse-risk (n = 444; 13%; 95% CI, 8-20) AML.
In a multivariable analysis, allogeneic HSCT appeared associated with better 5-year OS (HR = 0.71; 95% CI, 0.53-0.95) compared with non-allogeneic HSCT post-remission therapies or with no further treatment, especially among patients with intermediate-risk (HR = 0.82; 95% CI, 0.58-1.15) or adverse-risk (HR = 0.39; 95% CI, 0.21-0.73) AML.
The researchers acknowledged the inclusion of only a small number of allogeneic HSCT patients in their analysis as a study limitation.
“Although transplant decisions should be based on a careful pre-transplant risk assessment of relapse and non-relapse mortality, these results suggest that the early search and identification of a compatible donor should also be pursued in elderly patients with an adverse AML risk profile,” Cornelissen and colleagues wrote.
It remains uncertain whether allogeneic HSCT will be generally accepted as a standard practice for older patients with AML, Marcos de Lima, MD, director of bone marrow transplantation at University Hospitals Case Medical Center and professor of medicine at Case Western Reserve University Medical School in Cleveland, wrote in an accompanying editorial.
“HSCTs are rarely done or recommended for patients older than 70 to 75 years of age, and registry data suggest that this approach is widespread,” de Lima wrote. “Whether or not this will change is unclear, but I would speculate that with existing approaches, standard allogeneic transplantation will not have a major role for individuals in the eighth to ninth decades of life. However, new cellular therapy treatment options might change that.” – by Cameron Kelsall
Disclosure: The researchers report no relevant financial disclosures. de Lima reports consultant roles with Celgene and Seattle Genetics.
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