Intensive Consolidation Treatment Prior to Allogeneic Stem-Cell Transplantation: Does It Really Improve Outcomes in Older Patients with Acute Myeloid Leukemia?

In older patients with acute myeloid leukemia (AML), the use of intensive consolidation treatment prior to allogeneic stem-cell transplantation has been a matter of debate. A recent retrospective comparison study aimed to evaluate whether intensive consolidation therapy improves outcomes in this patient population. However, the study’s findings did not demonstrate any significant benefits of intensive consolidation therapy. This article critically analyzes the study’s methodology, results, and implications, highlighting alternative approaches that may improve pretransplant status for older patients with AML.

The Study

The study included 130 patients over the age of 60 who were in the first complete remission (CR) and underwent allogeneic stem-cell transplantation for AML between 2007 and 2017. Out of these patients, 68 received intensive pretransplant consolidation therapy, while 62 received a non-intensive regimen. The primary outcomes evaluated were relapse-free survival (RFS) and overall survival (OS) at the 2-year mark following stem-cell transplant.

Upon analyzing the data, the study found that the 2-year RFS was nearly identical for both groups, with 51% in the intensive-therapy group and 50% in the non-intensive therapy group. This lack of difference in RFS between the two groups suggests that intensive consolidation treatment did not significantly improve outcomes. Although the intensive-therapy group showed a trend towards worse non-relapse mortality, this difference was not statistically significant.

Similarly, the study did not find any significant differences in OS or rates of acute and chronic graft-versus-host disease (GVHD) between the two groups. These findings challenge the notion that intensive consolidation therapy is essential for improving outcomes in older patients with AML undergoing allogeneic stem-cell transplantation.

Given the negative findings of the study, it is crucial to explore alternative approaches that may enhance the pretransplant status of older AML patients. Yosr Hicheri, MD, of Institut Paoli Calmettes in Marseilles, France, suggested four promising approaches:

Newer Drugs

Various newer drugs, such as FLT3 inhibitors, CPX-351, and inhibitors of IDH, have revolutionized the landscape of AML therapeutics. Further investigation and utilization of these drugs may offer improved outcomes for older AML patients undergoing stem-cell transplantation.

Venetoclax with Azacitidine

The combination of Venetoclax (Venclexta) with azacitidine, followed by stem-cell transplant, has shown excellent outcomes in newly diagnosed AML patients older than 60. This combination therapy may provide superior results compared to maintenance therapy.

Nonmyeloablative Haploidentical Stem-Cell Transplant

Nonmyeloablative haploidentical stem-cell transplant with peripheral blood cells and post-transplant cyclophosphamide has demonstrated excellent tolerance and long-term survival in elderly patients with AML or myelodysplastic syndromes (MDS). This approach warrants further investigation as an alternative to intensive consolidation therapy.

The study’s findings suggest that intensive consolidation treatment prior to allogeneic stem-cell transplantation does not significantly improve outcomes in older patients with AML. This challenges the conventional perception and emphasizes the need for alternative approaches to enhance pretransplant status. By focusing on newer drugs, Venetoclax with azacitidine, and nonmyeloablative haploidentical stem-cell transplantation, clinicians can explore potentially more effective therapies. Further research and clinical trials are necessary to elucidate the optimal treatment strategies for this patient population and improve their overall outcomes.

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