FLAMSA versus busulfan/fludarabine conditioning for acute myeloid leukemia patients

On behalf of the Acute Leukemia Working Party (ALWP) of the EBMT, Thomas Heinicke from Otto-von-Guericke University, Magdeburg, Germany, and colleagues retrospectively analyzed outcomes of acute myeloid leukemia (AML) patients in first or second complete remission (CR1 or CR2) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) after busulfan/fludarabine (BuFlu), sequential FLAMSA (fludarabine + Ara-C + amsacrine chemotherapy) followed by either cyclophosphamide plus total body irradiation (FLAMSA-TBI) or cyclophosphamide plus busulfan (FLAMSA-Bu) conditioning. The study was published ahead of print in Biology of Bone and Marrow Transplantation.

Data was collected from the ALWP of the EBMT registry. Patients with AML undergoing allo-HSCT in CR1 or CR2 between January 2005 and June 2016 were included in the analysis. Patients received either BuFlu (n = 1,197; median age = 58.8 years [range, 20.1–76]) or FLAMSA-TBI (n = 258; median age = 47 years [range, 18.1–66.8]) or FLAMSA-Bu (n = 141; median age = 59.6 years [range, 19.6–74.4]).

The primary endpoint of the study was leukemia-free survival (LFS). Secondary endpoints included overall survival (OS), refined graft-versus-host-disease-free survival, relapse-free survival (GRFS), neutrophil engraftment, acute and chronic graft-versus-host disease (GvHD), relapse incidence (RI), and non-relapse mortality (NRM).

Key findings:

• Median follow-up: 24.72 months
• BuFlu vs FLAMSA-TBI vs FLAMSA-Bu groups:
  • 2-year LFS: 53.6% vs 61.6% vs 50.1%, P = 0.03
  • 2-year OS: 60% vs 68.3% vs 56.4%, N.S
  • GRFS: 40.2% vs 46.9% vs 38.1%, N.S
  • Neutrophil engraftment: 99.75% vs 97.7% vs 97.1%, P < 0.001
  • RI: 30.3% vs 21.9% vs 23.1%, P < 0.01
  • 2-year NRM: 16.1% vs 16.4% vs 26.7%, P < 0.01
• Cumulative incidence of acute GvHD grade II–IV and grade II–IV by day 100 after allo-SCT: 22.9% (95% CI, 20.8–20.5) and 9.1 (95% CI, 7.7–10.6), respectively
• Acute GvHD in the BuFlu and the FLAMSA cohort: 21.1% vs 26.9%, P < 0.001
• 2-year cumulative incidence of chronic GvHD: 34% (95% CI, 31.4–36.5)
• FLAMSA-TBI compared with BuFlu showed lower relapse incidence (RI): HR = 0.64 (95% CI, 0.42–0.98), P = 0.04
• FLAMSA-TBI compared with BuFlu showed superior LFS: HR = 0.72 (95% CI, 0.49–1.06), P = 0.09

Taken together, these findings showed that FLAMSA-TBI leads to lower relapse incidence in comparison with BuFlu in AML patients transplanted in CR1 or CR2. The key limitations of this study include its retrospective nature as well as the heterogeneity of the administered GvHD prophylaxis. The authors stated that prospective studies are required to further evaluate the FLAMSA regimen.

References

1. Heinicke T. et al. Reduced Relapse Incidence with FLAMSA-RIC conditioning compared to Busulfan/Fludarabine for AML-patients in first or second complete remission - A Study from the Acute Leukemia Working Party of the EBMT. Biol Blood Marrow Transplant. 2018 Jul 12. DOI: 1016/j.bbmt.2018.07.007. [Epub ahead of print].