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CLL: ibrutinib and transplantation ride together

Bone Marrow Transplantation volume 51, pages 769–770 (2016)Cite this article

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Much as it happened with CML, targeted therapies are challenging the role of allogeneic hematopoietic cell transplantation (alloHCT) in the treatment of CLL. Despite alloHCT being the only curative therapy for CLL, its broad implementation is limited by significant toxicity, a long-term procedure-related mortality of around 15–25%, the availability of a fully-matched donor and the advanced age of most patients with the disease. As a result, and not surprisingly, around 30% of patients with CLL in whom allogeneic stem cell transplantation is considered as a treatment possibility are not eventually transplanted.1 In contrast, targeted therapies such as B-cell receptor inhibitors (BCRi) (ibrutinib, idelalisib) or B-cell lymphoma 2 (BCL2) antagonists (venetoclax), albeit not curative, can be given to a wide range of patients and provide results comparable to those of alloHCT with much lower toxicity.2 Of note, treatment results with BCRi and BCL2 antagonists are likely to improve by combining these agents among themselves and/or with monoclonal antibodies.2, 3 Those facts led investigators from the European Society for Bone Marrow Transplantation (EBMT) and the European Research Initiative on CLL to refine EBMT prior recommendations and to restrict alloHCT to selected patients previously treated with one of these agents.4 The question we face now is: should targeted therapies replace alloHCT entirely?

Ample evidence shows that alloHCT is able to eradicate (cure) the disease, even in the presence of poor prognostic features (for example, TP53 disruption), although it works best when the disease is under control.5 Even with reduced-intensity conditioning regimes (which have replaced fully mieloblative conditioning in CLL allotransplantation) toxicity is considerable, mostly due to GvHD and infections, although it tends to decrease over time, and disease relapse is rare 4 years after transplantation. In turn, targeted therapies achieve remarkable and sustained responses, but hardly ever eradicate the disease. Of note, patients with TP53 disruption receiving these agents have an inferior long-term outcome compared with patients devoid of this genomic aberration.6 Survival curves of patients on these agents do not show a plateau, whereas the incidence of class-specific toxic effects (for example, hypertension and atrial fibrillation for ibrutinib; colitis, transaminitis and pneumonitis for idelalisib) apparently remains constant over time. Importantly, a longer follow-up of patients treated with targeted therapies is needed to better define, based on solid ground, the position of these agents in CLL treatment algorithms.

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  1. Department of Hematology Hospital Clinic, Institute of Hematology and Oncology, University of Barcelona, Barcelona, Spain

    E Montserrat & J Delgado

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  1. E Montserrat
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Correspondence to E Montserrat.

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Montserrat, E., Delgado, J. CLL: ibrutinib and transplantation ride together. Bone Marrow Transplant 51, 769–770 (2016). https://doi.org/10.1038/bmt.2016.118

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