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Durable benefit of rituximab maintenance post-autograft in patients with relapsed follicular lymphoma: 12-year follow-up of the EBMT lymphoma working party Lym1 trial

Bone Marrow Transplantation volume 56, pages 1413–1421 (2021)Cite this article

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Abstract

We report the 12-year follow-up of the prospective randomized EBMT LYM1 trial to determine whether the benefit of brief duration rituximab maintenance (RM) on progression-free survival (PFS) in patients with relapsed follicular lymphoma (FL) receiving an autologous stem cell transplant (ASCT) is sustained. One hundred and thirty-eight patients received RM with or without purging. The median follow-up after random assignment is 12 years (range 10–13) for the whole series. The 10-year PFS after ASCT is 47% (95% CI 40–54) with only 4 patients relapsing after 7.5 years. RM continues to significantly improve 10-year PFS after ASCT in comparison with NM [P = 0.002; HR 0.548 (95% CI 0.38–0.80)]. Ten-year non-relapse mortality (NRM) was not significantly different between treatment groups (7% overall). 10-year overall survival (OS) after ASCT was 75% (69–81) for the whole series, with no significant differences according to treatment sub-groups. 10-year OS for patients who progressed within 24 months (POD24T) was 60%, in comparison with 85% for patients without progression. Thus the benefit of rituximab maintenance after ASCT on relapse prevention is sustained at 12 years, suggesting that RM adds to ASCT-mediated disease eradication and may enhance the curative potential of ASCT.

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Fig. 1: Patient disposition.
Fig. 2: Incidence of relapse post transplantation of RM or NM.
Fig. 3: Progression Free Survival (PSF) and Overall Survival (OS) from the date of autologous stem cell transplantation (ASCT).
Fig. 4: Progression free survival by treatment arm.
Fig. 5: OS by disease progression at 24 months from date of transplant (POD24).

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Acknowledgements

We thank all the investigators who contributed to this work and provided data updates for the purpose of this analysis. We thank all the EBMT trials office staff who have contributed to the conduct of this trial. We also thank the patients who agreed to participate in this study. This study was supported by an unrestricted educational grant from Roche Ltd. P.F. Abellan, N. Blesing, J.-H. Bourhis, G. Cook, P. Colombat, E. Conde, S.J.B. De Laguna, J. De La Serna, R. Evely, M. Fabbro, P. Fields, P. Forsyth, C. Fruchart, J. Gabarre, J. Gibson, R.V. Gilleece, MH. Gomez, U. Graeven, R. Gressin, P. Guardiola, T. Gumbleton, C. Hatton, T. Hawkins, W. Jung, H. Johnsen, Y. Kerneis, S. Killick, C. Kulecki, T. Lamy, A. Lange, P. Lederlin, X. Levaltier, S. Al-Ismail, T.A. Lopez, M.P.A. R. Lush, Lyttelton, M.P. Macheta, H. Maisonneuve, R. Marcus, A. McMillan, G. McQuaker, D. Milligan, T. Mills, C. Morris, M. Nickelsen, F. Offner, J.M. Ojanguren, M.J. Penarrubia, A.R. Pettit, H. Pflueger, H. Pullon, K.- A. Robertson. Rotermund, R. A. Saenz, S. Sadullah, G. Salles, J.M.R. Santasusana, G. Schlimok, J. Seale, C. Sebban, J. Sierra, J. G. Smith, Snowden, L.G. Steven, D. Stewart, J. Szer, J.E. Tighe, N. Trehet, G.E. Turner, I. Valji, D. Wright.

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Authors and Affiliations

  1. Institute of Medical & Biomedical Education, St George’s University of London, London, United Kingdom

    R. Pettengell

  2. EBMT Clinical Trials Office, European Society for Blood and Marrow Transplantation, London, United Kingdom

    R. Uddin

  3. Statistics, European Society for Blood and Marrow Transplantation, Paris, France

    A. Boumendil

  4. Department of Haematology, St James’s University Hospital, Leeds, United Kingdom

    R. Johnson

  5. University Clinic for Internal Medicine, Oncology and Haematology, Klinikum Oldenburg, Oldenburg, Germany

    B. Metzner

  6. Hematology Department, Hospital Universitario de Salamanca, IBSAL, CIBERONC, Salamanca, Spain

    A. Martín

  7. Department of Lymphoproliferative Diseases, Maria Sklodowska-Curie Memorial Institute and Oncology Center, Warsaw, Poland

    J. Romejko-Jarosinska

  8. The University of Ottawa, The Ottawa Hospital, Ottawa, Canada

    I. Bence-Bruckler

  9. Haematology, Royal Adelaide Hospital, Adelaide, Southern Australia, Australia

    P. Giri

  10. Department of Hematology, Rigshospitalet, Copenhagen, Denmark

    C. U. Niemann

  11. Department of Haematology, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom

    S. P. Robinson

  12. Department of Hematology, Karolinska Institute, Stockholm, Sweden

    E. Kimby

  13. Department of Internal Medicine A, University Hospital Muenster, Muenster, Germany

    N. Schmitz

  14. Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany

    P. Dreger

  15. University College London Hospital, London, United Kingdom

    A. H. Goldstone

  16. Department of Haemato-oncology, St Bartholomew’s Hospital, Barts Health NHS Trust, London, United Kingdom

    S. Montoto

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Contributions

Conception and design: RP, AHG, AB, PD, SM. Provision of study materials or patients: RP, RU, SPR, RJ, TH, BM, AM, JRJ, IBB, PG, CN, EK, AHG. Collection and assembly of data: RP, AB, SM. Statistical analysis: AB. Interpretation of data and results: RP, SM. Paper writing: RP, SM, Final approval of paper: RP, RU, AB, RJ, BM, AM, JAJ, IBB, PG, CUN, SPR, EK, NS, PD, AHG, SM. All authors had full access to the raw data in the study and the corresponding author had final responsibility for the decision to submit for publication. RP, MDD, DA, DB, PG, DQ and GS enrolled patients, performed the study and analyzed the data, read and approved the paper. JWS, SBS, AE and CG contributed to study design, implementation, analysis of results, and preparation of the paper.

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Correspondence to R. Pettengell.

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Pettengell, R., Uddin, R., Boumendil, A. et al. Durable benefit of rituximab maintenance post-autograft in patients with relapsed follicular lymphoma: 12-year follow-up of the EBMT lymphoma working party Lym1 trial. Bone Marrow Transplant 56, 1413–1421 (2021). https://doi.org/10.1038/s41409-020-01182-w

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