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Letters to the Editor

The addition of ofatumumab to the conditioning regimen does not improve the outcome of patients with high-risk CLL undergoing reduced intensity allogeneic haematopoietic cell transplantation: a pilot trial from the GETH and GELLC (CLL4 trial)

Bone Marrow Transplantation volume 51, pages 1404–1407 (2016)Cite this article

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Patients with CLL whose tumour cells harbour a 17p deletion or TP53 mutation, or relapsing within 2 years of the previous chemoimmunotherapy regimen, are considered to have an adverse prognosis with conventional agents.1, 2 These patients have been traditionally offered allogeneic haematopoietic cell transplantation (alloHCT) according to EBMT guidelines.3 The addition of rituximab to the typical fludarabine-based reduced intensity-conditioning regimen has apparently improved the outcome of patients with CLL undergoing alloHCT.4, 5 Ofatumumab is a novel anti-CD20 monoclonal antibody with enhanced anti-CLL activity in vitro compared with rituximab,6 and has also shown clinical activity regardless of prior exposure to rituximab.7 In this investigator-initiated trial sponsored by the Grupo Español de Trasplante Hematopoyético (GETH) and Grupo Español de Leucemia Linfocítica Crónica (GELLC), we hypothesised that the addition of ofatumumab to the conditioning regimen of patients with CLL undergoing alloHCT could improve their outcome. This study was registered at clinicaltrials.gov (NCT01455051) and performed in accordance with the Declaration of Helsinki and the International Conference on Harmonised Guidelines for Good Clinical Practice. Ofatumumab was provided free of charge together with an unrestricted grant from GSK/Novartis.

Patients with CD20-positive CLL were eligible in the case of 17p deletion (17pD), disease refractory or relapse within 12 months of the last chemoimmunotherapy regimen (RR12). Patients had to be older than 18 and younger than 70 years old, have normal organ function and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2. The disease had to be in complete or partial response at the time of transplantation. Patients were excluded from this trial in the case of concomitant malignancy, active central nervous system (CNS) disease, active infection requiring intravenous antibiotics, prior alloHCT, pregnancy, breastfeeding, known hypersensitivity to ofatumumab or chronic infection by hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV). Donors were siblings or unrelated volunteers with 9–10/10 HLA compatibility at the molecular level (10/10). The primary end point of the study was PFS at 3 years.

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Authors and Affiliations

  1. Department of Haematology, Hospital La Fe, Valencia, Spain

    P Montesinos & J Sanz

  2. Department of Haematology, Hospital Clínico, Salamanca, Spain

    M Cabrero & D Caballero

  3. Department of Haematology, Hospital Vall d’Hebron, Barcelona, Spain

    D Valcárcel & P Abrisqueta

  4. Department of Haematology, Hospital Clínic, IDIBAPS, Barcelona, Spain

    M Rovira & J Delgado

  5. Department of Haematology, Hospital Puerta de Hierro, Majadahonda, Spain

    J A García-Marco

  6. Department of Haematology, Hospital Universitario de La Princesa, IIS-IP, Madrid, Spain

    J Loscertales

  7. Department of Haematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    C Moreno

  8. Department of Haematology, Hospital Duran i Reynals, L’Hospitalet de Llobregat, Spain

    R Duarte

  9. Department of Haematology, Hospital Clínic, Valencia, Spain

    M J Terol

  10. Haematopathology Unit, Hospital Clínic, IDIBAPS, Barcelona, Spain

    N Villamor

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  1. P Montesinos
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  14. J Delgado
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Corresponding author

Correspondence to J Delgado.

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Competing interests

This clinical trial was performed thanks to an unrestricted grant from GSK/Novartis. DV, JAG-M, JL, CM, MJT and JD have received consulting and lecturing fees from GSK/Novartis.

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Supplementary Information accompanies this paper on Bone Marrow Transplantation website

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Montesinos, P., Cabrero, M., Valcárcel, D. et al. The addition of ofatumumab to the conditioning regimen does not improve the outcome of patients with high-risk CLL undergoing reduced intensity allogeneic haematopoietic cell transplantation: a pilot trial from the GETH and GELLC (CLL4 trial). Bone Marrow Transplant 51, 1404–1407 (2016). https://doi.org/10.1038/bmt.2016.145

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