Deepa Jagadeesh1, Navneet S Majhail2, Yizeng He3, Kwang W Ahn3,4, Carlos Litovich4, Sairah Ahmed5, Mahmoud Aljurf6, Ulrike Bacher7, Sherif M Badawy8,9, Nelli Bejanyan10, Mitchell Cairo11, Jan Cerny12, Narendranath Epperla13, Nosha Farhadfar14, César O Freytes15, Robert Peter Gale16, Bradley Haverkos17, Nasheed Hossain18, David Inwards19, Rammurti T Kamble20, Vaishalee P Kenkre21, Hillard M Lazarus22, Aleksandr Lazaryan10, Lazaros Lekakis23, Matthew Mei24, Hemant S Murthy25, Alberto Mussetti26,27, Sunita Nathan28, Taiga Nishihori10, Richard F Olsson29,30, Praveen Ramakrishnan Geethakumari31, Bipin N Savani32, Jean A Yared33, Timothy S Fenske34, Mohamed A Kharfan-Dabaja25, Anna Sureda26,27, Mehdi Hamadani4. 1. Cleveland Clinic Foundation, Cleveland, Ohio. 2. Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio. 3. Division of Biostatistics, Institute of Health and Equity, Medical College of Wisconsin, Milwaukee, Wisconsin. 4. CIBMTR, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. 5. University of Texas MD Anderson Cancer Center, Houston, Texas. 6. Department of Oncology, King Faisal Specialist Hospital Center & Research, Riyadh, Saudi Arabia. 7. Department of Hematology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 8. Division of Hematology, Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois. 9. Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 10. Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida. 11. Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, New York Medical College, Valhalla, New York. 12. Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical Center, Worcester, Massachusetts. 13. Division of Hematology, Department of Medicine, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio. 14. Division of Hematology/Oncology, University of Florida College of Medicine, Gainesville, Florida. 15. Texas Transplant Institute, San Antonio, Texas. 16. Hematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom. 17. University of Colorado Hospital, Aurora, Colorado. 18. Division of Hematology/Oncology, Department of Medicine, Stem Cell Transplant Program, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois. 19. Division of Hematology, Mayo Clinic, Rochester, Minnesota. 20. Division of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas. 21. Division of Hematology/Oncology, University of Wisconsin, Madison, Wisconsin. 22. Divsion of Hematology/Oncology, Case Western Reserve University, Cleveland, Ohio. 23. Department of Hematology/Oncology, University of Miami, Miami, Florida. 24. Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, California. 25. Division of Hematology Oncology, Blood and Marrow Transplantation Program, Mayo Clinic Florida, Jacksonville, Florida. 26. Hematology Department, Institut Catalá d'Oncologia-Hospitalet, Barcelona, Spain. 27. IDIBELL-Institut Català d'Oncologia, l'Hospitalet de Llobregat, El Prat de Llobregat, Spain. 28. Division of Hematology, Oncology and Cell Therapy, Rush University Medical Center, Chicago, Illinois. 29. Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. 30. Centre for Clinical Research Sormland, Uppsala University, Uppsala, Sweden. 31. Lymphoma, BMT and Cellular Therapy Program, University of Texas Southwestern Medical Center, Dallas, Texas. 32. Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. 33. Blood & Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, Maryland. 34. Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
Abstract
BACKGROUND: Although rituximab-based high-dose therapy is frequently used in diffuse large B cell lymphoma (DLBCL) patients undergoing autologous hematopoietic cell transplantation (auto-HCT), data supporting the benefits are not available. Herein, we report the impact of rituximab-based conditioning on auto-HCT outcomes in patients who have DLBCL. METHODS: Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, 862 adult DLBCL patients undergoing auto-HCT between 2003 and 2017 using BEAM (BCNU, etoposide, cytarabine, melphalan) conditioning regimen were included. All patients received frontline rituximab-containing chemoimmunotherapy and had chemosensitive disease pre-HCT. Early chemoimmunotherapy failure was defined as not achieving complete remission (CR) after frontline chemoimmunotherapy or relapse within 1 year of initial diagnosis. The primary outcome was overall survival (OS). RESULTS: The study cohort was divided into 2 groups: BEAM (n = 667) and R-BEAM (n = 195). On multivariate analysis, no significant difference was seen in OS (P = .83) or progression-free survival (PFS) (P = .61) across the 2 cohorts. No significant association between the use of rituximab and risk of relapse (P = .15) or nonrelapse mortality (P = .12) was observed. Variables independently associated with lower OS included older age at auto-HCT (P < .001), absence of CR at auto-HCT (P < .001) and early chemoimmunotherapy failure (P < .001). Older age (P < .0002) and non-CR pre-HCT (P < .0001) were also associated with inferior PFS. There was no significant difference in early infectious complications between the 2 cohorts. CONCLUSION: In this large registry analysis of DLBCL patients undergoing auto-HCT, the addition of rituximab to the BEAM conditioning regimen had no impact on transplantation outcomes. Older age, absence of CR pre auto-HCT, and early chemoimmunotherapy failure were associated with inferior survival.
BACKGROUND: Although rituximab-based high-dose therapy is frequently used in diffuse large B cell lymphoma (DLBCL) patients undergoing autologous hematopoietic cell transplantation (auto-HCT), data supporting the benefits are not available. Herein, we report the impact of rituximab-based conditioning on auto-HCT outcomes in patients who have DLBCL. METHODS: Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, 862 adult DLBCL patients undergoing auto-HCT between 2003 and 2017 using BEAM (BCNU, etoposide, cytarabine, melphalan) conditioning regimen were included. All patients received frontline rituximab-containing chemoimmunotherapy and had chemosensitive disease pre-HCT. Early chemoimmunotherapy failure was defined as not achieving complete remission (CR) after frontline chemoimmunotherapy or relapse within 1 year of initial diagnosis. The primary outcome was overall survival (OS). RESULTS: The study cohort was divided into 2 groups: BEAM (n = 667) and R-BEAM (n = 195). On multivariate analysis, no significant difference was seen in OS (P = .83) or progression-free survival (PFS) (P = .61) across the 2 cohorts. No significant association between the use of rituximab and risk of relapse (P = .15) or nonrelapse mortality (P = .12) was observed. Variables independently associated with lower OS included older age at auto-HCT (P < .001), absence of CR at auto-HCT (P < .001) and early chemoimmunotherapy failure (P < .001). Older age (P < .0002) and non-CR pre-HCT (P < .0001) were also associated with inferior PFS. There was no significant difference in early infectious complications between the 2 cohorts. CONCLUSION: In this large registry analysis of DLBCL patients undergoing auto-HCT, the addition of rituximab to the BEAM conditioning regimen had no impact on transplantation outcomes. Older age, absence of CR pre auto-HCT, and early chemoimmunotherapy failure were associated with inferior survival.
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