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 journalArticle

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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B-Cell Chronic Lymphocytic Leukemia
Therapeutics
T-Cell Antigen Receptor
Aberrations
Phosphotransferases
Cell Transplantation
Availability
Pharmacology

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High-risk chronic lymphocytic leukemia in the era of pathway inhibitors: Integrating molecular and cellular therapies. / Dreger, P; Ghia, P; Schetelig, J; Van Gelder, M; Kimby, E; Michallet, M; Moreno, C; Robak, T; Stilgenbauer, S; Montserrat, E; (ERIC), on behalf of the European Research Initiative on CLL; Blood, the European Society for; (EBMT), Marrow Transplantation.

In: Blood, Vol. 132, No. 9, 2018, p. 892-902.

Research output: Contribution to journalArticle

Dreger, P, Ghia, P, Schetelig, J, Van Gelder, M, Kimby, E, Michallet, M, Moreno, C, Robak, T, Stilgenbauer, S, Montserrat, E, (ERIC), OBOTERIOCLL, Blood, TESF & (EBMT), MT 2018, 'High-risk chronic lymphocytic leukemia in the era of pathway inhibitors: Integrating molecular and cellular therapies', Blood, vol. 132, no. 9, pp. 892-902. https://doi.org/10.1182/blood-2018-01-826008
Dreger, P ; Ghia, P ; Schetelig, J ; Van Gelder, M ; Kimby, E ; Michallet, M ; Moreno, C ; Robak, T ; Stilgenbauer, S ; Montserrat, E ; (ERIC), on behalf of the European Research Initiative on CLL ; Blood, the European Society for ; (EBMT), Marrow Transplantation. / High-risk chronic lymphocytic leukemia in the era of pathway inhibitors: Integrating molecular and cellular therapies. In: Blood. 2018 ; Vol. 132, No. 9. pp. 892-902.
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AB - 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.

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