CLL: ibrutinib and transplantation ride together

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?