Rituximab-based allogeneic transplant for chronic lymphocytic leukemia with comparison to historical experience

• Type of Material: Article
• Authors: Mayzar Shadman, University of Washington; David G. Maloney, University of Washington; Barry Storer, University of Washington; Brenda M. Sandmaier, University of Washington; Thomas R. Chauncey, University of Washington; Niels Smedegaard Andersen, Finsen Center, Rigshospitalet, Copenhagen, Denmark; Dietger Niederwieser, Leipzig University; Judith Shizuru, Stanford University; Benedetto Bruno, University of Torino; Michael A. Pulsipher, Childrens Hospital Los Angeles; Richard T. Maziarz, Oregon Health and Science University; Edward D. Agura, Baylor University; Parameswaran Hari, Medical College of Wisconsin; Amelia Langston, Emory University; Michael B. Maris, Colorado Blood Cancer Institute; Peter A. McSweeney, Colorado Blood Cancer Institute; Rainer Storb, Fred Hutchinson Cancer Research Center; Mohamed L. Sorror, Fred Hutchinson Cancer Research Center
• Language: English
• Date: 2020-01-01
• Publisher: Nature Publishing Group
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020 Springer Nature Limited
• Final Published Version (URL): http://dx.doi.org/10.1038/s41409-019-0660-8
• Title of Journal or Parent Work: Bone Marrow Transplantation
• Volume: 55
• Issue: 1
• Start Page: 172
• End Page: 181
• Grant/Funding Information: Research reported in this manuscript was supported by the National Cancer Institute of the National Institutes of Health under award number P01 CA078902, P01 CA018029, P30 CA015704, and by the National Heart, Lung, and Blood Institute under K99/R00 HL088021 (M.L.S.).
• Keywords: Transplantation; Biophysics; Apoptosis; Hematopoietuc cell transplantation; Oncology; T-cells; Life Sciences & Biomedicine; Diagnosis; Hematology; Follow-up; Venetoclax; High-risk CLL; Guidelines; Immunology; Science & Technology
• Research Categories: Health Sciences, Oncology; Biology, Cell; Health Sciences, Immunology; Biophysics, Medical

Abstract

Relapse of chronic lymphocytic leukemia (CLL) after allogeneic hematopoietic cell transplantation (HCT) remains a clinical challenge. We studied in a phase II trial whether the addition of peri-transplant rituximab would reduce the relapse risk compared with historical controls (n = 157). Patients (n = 55) received fludarabine and low-dose total body irradiation combined with rituximab on days −3, + 10, + 24, + 36. Relapse rate at 3 years was significantly lower among rituximab-treated patients versus controls (17% versus 31%; P = 0.04). Overall survival (OS), progression-free survival (PFS) and nonrelapse mortality (NRM) were statistically similar: (53% versus 50%; P = 0.8), (44% versus 42%; P = 0.63), and (38% versus 28%; P = 0.2), respectively. In multivariate analysis, rituximab treatment was associated with lower relapse rates both in the overall cohort [hazard ratio (HR): 0.34, P = 0.006] and in patients with high-risk cytogenetics (HR: 0.21, P = 0.0003). Patients with no comorbidities who received rituximab conditioning had an OS rate of 100% and 75% at 1 and 3 years, respectively, with no NRM. Peri-transplant rituximab reduced relapse rates regardless of high-risk cytogenetics. HCT is associated with minimal NRM in patients without comorbidities and is a viable option for patients with high-risk CLL. Clinical trial information: NCT00867529.