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

Bone Marrow Transplantation volume 55, pages 172–181 (2020)Cite this article

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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.

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Acknowledgements

We would like to thank Helen Crawford for her assistance with paper/figure preparations.

Funding

Research reported in this paper 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 (MLS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, which had no involvement in the study design; the collection, analysis and interpretation of data; the writing of the report; nor in the decision to submit the article for publication.

Author contributions

MS, DGM, BS, BMS, RS, and MLS designed the study; MS, BS, and MLS performed the data analysis and interpretation, all authors contributed to data collection, writing and final approval of the paper.

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Authors and Affiliations

  1. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Mazyar Shadman, David G. Maloney, Barry Storer, Brenda M. Sandmaier, Thomas R. Chauncey, Rainer Storb & Mohamed L. Sorror

  2. University of Washington, Seattle, WA, USA

    Mazyar Shadman, David G. Maloney, Barry Storer, Brenda M. Sandmaier, Thomas R. Chauncey, Rainer Storb & Mohamed L. Sorror

  3. VA Puget Sound Healthcare System, Seattle, WA, USA

    Thomas R. Chauncey

  4. Department of Haematology, Finsen Center, Rigshospitalet, Copenhagen, Denmark

    Niels Smedegaard Andersen

  5. Division of Haematology and Medical Oncology, University of Leipzig, Leipzig, Germany

    Dietger Niederwieser

  6. Stanford University Medical Center, Stanford, CA, USA

    Judith Shizuru

  7. Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy

    Benedetto Bruno

  8. Division of Hematology, Oncology and Blood & Marrow Transplantation, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    Michael A. Pulsipher

  9. Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA

    Richard T. Maziarz

  10. Blood & Marrow Transplant Program, Baylor University Medical Center, Dallas, TX, USA

    Edward D. Agura

  11. Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA

    Parameswaran Hari

  12. Emory University, Winship Cancer Institute, Atlanta, GA, USA

    Amelia A. Langston

  13. Colorado Blood Cancer Institute, Denver, CO, USA

    Michael B. Maris & Peter A. McSweeney

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Correspondence to Mohamed L. Sorror.

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Conflict of interest

MS provided consultancy for Abbvie, Genentech, Astra Zeneca and Sound Biologics; has been on the advisory board for Abbvie, Genentech, Pharmacyclics, Astra Zeneca, ADC Therapeutics, Atara, and Verastem; and receives research funding from Mustang Biopharma, Pharmacyclics, Gilead, Genentech, TG Therapeutics, Bigene, Celgene, Acerta, Emergent, Sunesis and Merck. Otherwise, the authors declare that they have no conflict of interest.

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Shadman, M., Maloney, D.G., Storer, B. et al. Rituximab-based allogeneic transplant for chronic lymphocytic leukemia with comparison to historical experience. Bone Marrow Transplant 55, 172–181 (2020). https://doi.org/10.1038/s41409-019-0660-8

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