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

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 patient...

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Bibliographic Details
Published in:Blood 2018-08, Vol.132 (9), p.892-902
Main Authors: Dreger, Peter, Ghia, Paolo, Schetelig, Johannes, van Gelder, Michel, Kimby, Eva, Michallet, Mauricette, Moreno, Carol, Robak, Tadeusz, Stilgenbauer, Stephan, Montserrat, Emili, on behalf of the European Research Initiative on CLL (ERIC) and the European Society for Blood and Marrow Transplantation (EBMT)
Format: Article
Language:English
Subjects:
Adoptive Transfer
Allografts
Drug Resistance, Neoplasm - genetics
Drug Resistance, Neoplasm - immunology
Hematopoietic Stem Cell Transplantation
Humans
Leukemia, Lymphocytic, Chronic, B-Cell - genetics
Leukemia, Lymphocytic, Chronic, B-Cell - immunology
Leukemia, Lymphocytic, Chronic, B-Cell - mortality
Leukemia, Lymphocytic, Chronic, B-Cell - therapy
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Summary: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. [Display omitted]
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2018-01-826008