High-risk chronic lymphocytic leukemia in the era of pathway inhibitors: Integrating molecular and cellular therapies

P Dreger, P Ghia, J Schetelig, M Van Gelder, E Kimby, M Michallet, C Moreno, T Robak, S Stilgenbauer, E Montserrat, on behalf of the European Research Initiative on CLL (ERIC), the European Society for Blood, Marrow Transplantation (EBMT)

Research output: Contribution to journalArticlepeer-review

Abstract

High-risk chronic lymphocytic leukemia (CLL) has been defined by clinical and/or genetic resistance (TP53 abnormalities) to treatment with chemoimmunotherapy (CIT). With the availability of pathway inhibitors (PIs), such as kinase inhibitors and BCL2 antagonists, the outlook of CIT-resistant patients has dramatically improved. Here, we propose a revision of the concept of high-risk CLL, driven by TP53 abnormalities and response to treatment with PI. CLL high-risk-I, CIT-resistant is defined by clinically CIT-resistant disease with TP53 aberrations, but fully responsive to PI. This category is largely the domain of PI-based therapy, and cellular therapy (ie, allogeneic hematopoietic cell transplantation) remains an option only in selected patients with low individual procedure-related risk. In CLL high-risk-II, CIT- and PI-resistant, characterized by increasing exhaustion of pharmacological treatment possibilities, cellular therapies (including chimeric antigen receptor-engineered T cells) should be considered in patients eligible for these procedures. Moreover, molecular and cellular therapies are not mutually exclusive and could be used synergistically to exploit their full potential. © 2018 by The American Society of Hematology.
Original languageEnglish
Pages (from-to)892-902
Number of pages11
JournalBlood
Volume132
Issue number9
DOIs
Publication statusPublished - 2018

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