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Impact of Reduced-Intensity Conditioning Regimens on Outcomes in Diffuse Large B Cell Lymphoma Undergoing Allogeneic Transplantation.
Biol Blood Marrow Transplant. 2020 Sep 19 [Online ahead of print]BB

Abstract

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.

Authors+Show Affiliations

Division of Hematology, Department of Medicine, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio.Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, Wisconsin.Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, Wisconsin.Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.Division of Stem Cell Transplant and Cellular Therapy, Department of Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, North Carolina.Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic Florida, Jacksonville, Florida.Hematology Department, Institut Català d'Oncologia-Hospitalet, IDIBELL, University of Barcelona, Barcelona, Spain.Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: mhamadani@mcw.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32956819

Citation

Epperla, Narendranath, et al. "Impact of Reduced-Intensity Conditioning Regimens On Outcomes in Diffuse Large B Cell Lymphoma Undergoing Allogeneic Transplantation." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 2020.
Epperla N, Ahn KW, Khanal M, et al. Impact of Reduced-Intensity Conditioning Regimens on Outcomes in Diffuse Large B Cell Lymphoma Undergoing Allogeneic Transplantation. Biol Blood Marrow Transplant. 2020.
Epperla, N., Ahn, K. W., Khanal, M., Litovich, C., Ahm Ed, S., Ghosh, N., Fenske, T. S., Kharfan-Dabaja, M. A., Sureda, A., & Hamadani, M. (2020). Impact of Reduced-Intensity Conditioning Regimens on Outcomes in Diffuse Large B Cell Lymphoma Undergoing Allogeneic Transplantation. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation. https://doi.org/10.1016/j.bbmt.2020.09.014
Epperla N, et al. Impact of Reduced-Intensity Conditioning Regimens On Outcomes in Diffuse Large B Cell Lymphoma Undergoing Allogeneic Transplantation. Biol Blood Marrow Transplant. 2020 Sep 19; PubMed PMID: 32956819.
* Article titles in AMA citation format should be in sentence-case
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 - Ahm Ed,Sairah, AU - Ghosh,Nilanjan, AU - Fenske,Timothy S, AU - Kharfan-Dabaja,Mohamed A, AU - Sureda,Anna, AU - Hamadani,Mehdi, Y1 - 2020/09/19/ PY - 2020/07/17/received PY - 2020/08/18/revised PY - 2020/09/06/accepted PY - 2020/9/22/pubmed PY - 2020/9/22/medline PY - 2020/9/21/entrez KW - Allogeneic hematopoietic cell transplantation KW - Diffuse large B cell lymphoma KW - Reduced-intensity conditioning KW - Survival JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol Blood Marrow Transplant 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. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/32956819/Impact_of_reduced_intensity_conditioning_regimens_on_outcomes_in_diffuse_large_B_cell_lymphoma_undergoing_allogeneic_transplantation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(20)30579-6 DB - PRIME DP - Unbound Medicine ER -
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