Reduced intensity conditioning (RIC) with fludarabine plus melphalan significantly improves long-term overall survival (OS) and leukemia-free survival (LFS) compared with fludarabine plus busulfan in patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT), according to a report published in Blood Advances (2020;4(13):3180-3190. doi:10.1182/bloodadvances.2019001266).
“Fludarabine/melphalan… and fludarabine/busulfan… are the 2 most commonly used RIC regimens in HCT,” explained Zheng Zhou, MD, PhD, Beth Israel Lahey Health, Lahey Hospital and Medical Center, Burlington, Massachusetts, and colleagues.
“There have been several retrospective studies and a meta-analysis comparing the 2; however, these studies were limited by the inclusion of various age groups, disease-related factors, and graft-versus-host disease (GVHD) prophylaxis regimens,” they added.
In order to compare the 2 RIC regimens, researchers analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) on adult patients with AML who received allo-transplant between 2001 and 2015. Patients who received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion were excluded from the study.
The primary outcome was OS. Secondary outcomes included LFS, nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used to adjust for patient-, leukemia-, and transplant-related factors.
A total of 1413 patients were included in the analysis and received RIC with fludarabine plus melphalan (n = 622) or fludarabine plus busulfan (n = 791).
Patients in the fludarabine-melphalan group had fewer transplants in complete remission, fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab in comparison to those in the fludarabine-busulfan group. The fludarabine-melphalan group had more patients who received bone marrow grafts, as well as more patients who received transplants prior to 2005.
OS was significantly lower within the first 3 months after transplant in the fludarabine-melphalan group compared to the fludarabine-busulfan group (hazard ratio [HR] = 1.82, P <.001). However, OS was marginally superior beyond 3 months for those in the fludarabine-melphalan group (HR = 0.87, P = .05). Additionally, LFS was longer with fludarabine-melphalan compared to fludarabine-busulfan (HR = 0.89, P = .05).
During the first 3 months after transplant, NRM was significantly increased in the fludarabine-melphalan group (HR = 3.85, P <.001). However, long-term relapse was lower in this group compared to fludarabine-busulfan (HR = 0.65, P <.001).
“In conclusion, the results of this large comparative study from CIBMTR suggest that long-term OS and LFS are marginally superior with FM [fludarabine-melphalan] compared with FB [fludarabine-busulfan] regimen but at the expense of higher early NRM with FM,” Dr Zhou and colleagues concluded.—Janelle Bradley
