Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors

• Type of Material: Article
• Authors: Evgeny Klyuchnikov, University Cancer Center Hamburg; Ulrike Bacher, University of Göttingen; Nicolaus M. Kroeger, University Cancer Center Hamburg; Parameswaran N. Hari, Medical College of Wisconsin; Kwang Woo Ahn, Medical College of Wisconsin; Jeanette Carreras, Medical College of Wisconsin; Veronika Bachanova, University of Minnesota; Asad Bashey, Northside Hospital; Jonathon Cohen, Emory University; Anita D'Souza, Medical College of Wisconsin; César O. Freytes, South Texas Veterans Health Care System; Robert Peter Gale, Imperial College London; Siddhartha Ganguly, University of Kansas; Mark S. Hertzberg, Prince of Wales Hospital; Leona A. Holmberg, Fred Hutchinson Cancer Research Center; Mohamed A. Kharfan-Dabaja, H. Lee Moffitt Cancer Center and Research Institute; Andreas Klein, Tufts Medical Center; Grace H. Ku, University of California San Diego; Ginna G. Laport, Stanford Hospital & Clinics; Hillard M. Lazarus, University Hospitals Case Medical Center; Alan M. Miller, Baylor University; Alberto Mussetti, Fondazione IRCCS Istituto Nazionale dei Tumori; Richard F. Olsson, Karolinska Institutet; Shimon Slavin, International Center for Cell Therapy & Cancer Immunotherapy (CTCI); Saad Z. Usmani, Carolinas HealthCare System; Ravi Vij, Washington University; William A. Wood, University of North Carolina; David G. Maloney, Fred Hutchinson Cancer Research Center; Anna M. Sureda, Hospital Duran i Reynals, Spain; Sonali M. Smith, University of Chicago; Mehdi Hamadani, Medical College of Wisconsin
• Language: English
• Date: 2015-12-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 American Society for Blood and Marrow Transplantation.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbmt.2015.07.028
• Title of Journal or Parent Work: Biology of Blood and Marrow Transplantation
• ISSN: 1083-8791
• Volume: 21
• Issue: 12
• Start Page: 2091
• End Page: 2099
• Grant/Funding Information: For complete funding information, please see the full article.; The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research; and grants from various organizations and companies.
• Keywords: STEM-CELL TRANSPLANTATION; Reduced-intensity allogeneic hematopoietic cell transplantation; RELAPSE; EBMT; Hematology; HIGH-DOSE THERAPY; FOLLOW-UP; Science & Technology; ALLOGENEIC TRANSPLANTATION; AUTOLOGOUS TRANSPLANTATION; Immunology; PROGRESSION-FREE SURVIVAL; RITUXIMAB; Transplantation; Autologous hematopoietic cell transplantation; Long-time survival; NON-HODGKINS-LYMPHOMA; Life Sciences & Biomedicine; Grade 1 and 2 follicular lymphoma
• Research Categories: Health Sciences, Immunology; Health Sciences, Medicine and Surgery; Health Sciences, Oncology

Abstract

Purpose: Comparison of long-term outcomes in patients with refractory/relapsed grade 1-2 follicular lymphoma (FL) after allogeneic (allo-HCT) vs. autologous hematopoietic cell transplantation (auto-HCT) in the rituximab-era. Methods: Adult patients with relapsed/refractory grade 1-2 FL undergoing 1st reduced-intensity allo-HCT or 1st autograft during 2000-2012 were evaluated. Results: A total of 518 rituximab-treated patients were included. Allo-HCT patients were younger; more heavily pretreated, and more patients had advanced stage and chemoresistant disease. The 5-year adjusted probabilities, comparing auto- vs. allo-HCT groups for non-relapse mortality (NRM) were 5% vs. 26% (p<0.0001); relapse/progression: 54% vs. 20% (p<0.0001); progression-free survival (PFS): 41% vs. 58% (p<0.001) and overall survival (OS): 74% vs. 66% (p=0.05). Auto-HCT was associated with a higher risk of relapse/progression beyond 5 months post-HCT (RR=4.4; p<0.0001), and worse PFS (RR=2.9; p<0.0001) beyond 11 months post HCT. In the first 24 months post HCT, auto-HCT was associated with improved OS (RR=0.41; p<0.0001), but beyond 24 months with inferior OS (RR=2.2; p=0.006). A landmark analysis of patients alive and progression-free at 2-years post-HCT confirmed these observations, showing no difference in further NRM between both groups, but significantly higher risk of relapse/progression (RR=7.3; p<0.0001) and inferior PFS (RR=3.2; p<0.0001) and OS (RR=2.1; p=0.04) following auto-HCT. The 10-year cumulative incidence of second hematological malignancies following allo- and auto-HCT was 0% and 7%, respectively. Conclusion: Auto- and RIC-allo-HCT as 1st transplantation approach can provide durable disease control in grade 1-2 FL patients. Continued disease relapse-risk following auto-HCT translates into improved PFS and OS following allo-HCT, in long-term survivors.