TY - JOUR
T1 - Impact of Reduced-Intensity Conditioning Regimens on Outcomes in Diffuse Large B Cell Lymphoma Undergoing Allogeneic Transplantation
AU - Epperla, Narendranath
AU - Ahn, Kwang W.
AU - Khanal, Manoj
AU - Litovich, Carlos
AU - Ahmed, Sairah
AU - Ghosh, Nilanjan
AU - Fenske, Timothy S.
AU - Kharfan-Dabaja, Mohamed A.
AU - Sureda, Anna
AU - Hamadani, Mehdi
N1 - Publisher Copyright:
© 2020 American Society for Transplantation and Cellular Therapy
PY - 2020
Y1 - 2020
N2 - Reduced-intensity conditioning (RIC) regimens are frequently used for allogeneic hematopoietic cell transplantation (allo-HCT) in patients with diffuse large B cell lymphoma (DLBCL). However, the RIC regimen with the best risk/benefit profile for allo-HCT in DLBCL is not known. This is particularly important because patients with DLBCL undergoing allo-HCT in the future would be enriched for those whose lymphoma has failed chimeric antigen receptor T cell (CAR-T) therapy or other novel immunotherapies, with potentially more advanced disease and suboptimal performance scores. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we report the outcomes of the 3 most commonly used allo-HCT RIC regimens in patients with DLBCL. Our analysis included a total of 562 adult DLBCL patients in the CIBMTR registry undergoing allo-HCT using matched related or unrelated donors, between 2008 and 2016. Patients received 1 of 3 RIC regimens: fludarabine/i.v. busulfan ~6.4 mg/kg (Flu/Bu), fludarabine/melphalan 140 mg/m2 (Flu/Mel140), or BCNU/etoposide/cytarabine/melphalan (BEAM). Accordingly, the study group was divided into 3 groups: Flu/Bu (n = 151), Flu/Mel140 (n = 296), and BEAM (n = 115). Relative to Flu/Bu, the Flu/Mel140 (hazard ratio [HR], 2.33; 95% confidence interval [CI], 1.42 to 3.82; P =.001) and BEAM (HR, 2.54; 95% CI, 1.34 to 4.80; P =.004) regimens were associated with a risk of higher nonrelapse mortality (NRM). Although the risk of relapse with Flu/Mel140 was lower than that with Flu/Bu (HR,.70; 95% CI,.52 to.95; P =.02), this did not translate to improved progression-free survival (HR, 1.04) or overall survival (HR, 1.30). There was a significantly higher risk of grade III-IV acute graft-versus-host disease with BEAM compared with Flu/Bu (HR, 2.19; 95% CI, 1.10 to 4.35; P =.03). In the chemosensitive subset, multivariate analysis showed a significantly higher mortality risk with Flu/Mel140 (HR, 1.48; 95% CI, 1.07 to 2.04; P =.02) relative to Flu/Bu conditioning. In the largest analysis comparing the impact of various RIC regimens on the survival of DLBCL patients undergoing allo-HCT, our results suggest that Flu/Bu is a better RIC choice in less fit or heavily pretreated patients due to lowest NRM risk.
AB - Reduced-intensity conditioning (RIC) regimens are frequently used for allogeneic hematopoietic cell transplantation (allo-HCT) in patients with diffuse large B cell lymphoma (DLBCL). However, the RIC regimen with the best risk/benefit profile for allo-HCT in DLBCL is not known. This is particularly important because patients with DLBCL undergoing allo-HCT in the future would be enriched for those whose lymphoma has failed chimeric antigen receptor T cell (CAR-T) therapy or other novel immunotherapies, with potentially more advanced disease and suboptimal performance scores. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we report the outcomes of the 3 most commonly used allo-HCT RIC regimens in patients with DLBCL. Our analysis included a total of 562 adult DLBCL patients in the CIBMTR registry undergoing allo-HCT using matched related or unrelated donors, between 2008 and 2016. Patients received 1 of 3 RIC regimens: fludarabine/i.v. busulfan ~6.4 mg/kg (Flu/Bu), fludarabine/melphalan 140 mg/m2 (Flu/Mel140), or BCNU/etoposide/cytarabine/melphalan (BEAM). Accordingly, the study group was divided into 3 groups: Flu/Bu (n = 151), Flu/Mel140 (n = 296), and BEAM (n = 115). Relative to Flu/Bu, the Flu/Mel140 (hazard ratio [HR], 2.33; 95% confidence interval [CI], 1.42 to 3.82; P =.001) and BEAM (HR, 2.54; 95% CI, 1.34 to 4.80; P =.004) regimens were associated with a risk of higher nonrelapse mortality (NRM). Although the risk of relapse with Flu/Mel140 was lower than that with Flu/Bu (HR,.70; 95% CI,.52 to.95; P =.02), this did not translate to improved progression-free survival (HR, 1.04) or overall survival (HR, 1.30). There was a significantly higher risk of grade III-IV acute graft-versus-host disease with BEAM compared with Flu/Bu (HR, 2.19; 95% CI, 1.10 to 4.35; P =.03). In the chemosensitive subset, multivariate analysis showed a significantly higher mortality risk with Flu/Mel140 (HR, 1.48; 95% CI, 1.07 to 2.04; P =.02) relative to Flu/Bu conditioning. In the largest analysis comparing the impact of various RIC regimens on the survival of DLBCL patients undergoing allo-HCT, our results suggest that Flu/Bu is a better RIC choice in less fit or heavily pretreated patients due to lowest NRM risk.
KW - Allogeneic hematopoietic cell transplantation
KW - Diffuse large B cell lymphoma
KW - Reduced-intensity conditioning
KW - Survival
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U2 - 10.1016/j.bbmt.2020.09.014
DO - 10.1016/j.bbmt.2020.09.014
M3 - Article
C2 - 32956819
AN - SCOPUS:85093981145
SN - 1083-8791
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
ER -