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

doi:10.1182/blood-2018-01-826008

Review

. 2018 Aug 30;132(9):892-902.

doi: 10.1182/blood-2018-01-826008. Epub 2018 Jul 11.

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

Peter Dreger^{1

2}, Paolo Ghia^{3

4}, Johannes Schetelig^{2

5

6}, Michel van Gelder^{2

7}, Eva Kimby⁸, Mauricette Michallet⁹, Carol Moreno¹⁰, Tadeusz Robak¹¹, Stephan Stilgenbauer¹², Emili Montserrat^{4

13}; European Research Initiative on CLL (ERIC) and the European Society for Blood and Marrow Transplantation (EBMT)

Affiliations

¹ Department Medicine V, University of Heidelberg, Heidelberg, Germany.
² European Society for Blood and Marrow Transplantation, Leiden, The Netherlands.
³ Division of Experimental Oncology, Università Vita-Salute San Raffaele and IRCCS San Raffaele Scientific Institute, Milan, Italy.
⁴ European Research Initiative on CLL (ERIC), Barcelona, Spain.
⁵ Department Medicine I, University of Dresden, Dresden, Germany.
⁶ German Bone Marrow Donor Registry, Tübingen, Germany.
⁷ Department Internal Medicine/Hematology, Maastricht University, Maastricht, The Netherlands.
⁸ Department of Medicine/Center of Hematology at Karolinska Institute, Stockholm, Sweden.
⁹ Service d'Hématologie, Centre Léon Bérard, Lyon, France.
¹⁰ Hematology Department, Hospital de laSanta Creu i Sant Pau, Barcelona, Spain.
¹¹ Department of Hematology, Copernicus Memorial Hospital, Medical University of Lodz, Lodz, Poland.
¹² Department Medicine III, University of Ulm, Ulm, Germany; and.
¹³ Department of Hematology, Hospital Clínic, University of Barcelona, Barcelona, Spain.

PMID: 29997221
DOI: 10.1182/blood-2018-01-826008

Free article

Review

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

Peter Dreger et al. Blood. 2018.

Free article

. 2018 Aug 30;132(9):892-902.

doi: 10.1182/blood-2018-01-826008. Epub 2018 Jul 11.

Authors

Affiliations

¹ Department Medicine V, University of Heidelberg, Heidelberg, Germany.
² European Society for Blood and Marrow Transplantation, Leiden, The Netherlands.
³ Division of Experimental Oncology, Università Vita-Salute San Raffaele and IRCCS San Raffaele Scientific Institute, Milan, Italy.
⁴ European Research Initiative on CLL (ERIC), Barcelona, Spain.
⁵ Department Medicine I, University of Dresden, Dresden, Germany.
⁶ German Bone Marrow Donor Registry, Tübingen, Germany.
⁷ Department Internal Medicine/Hematology, Maastricht University, Maastricht, The Netherlands.
⁸ Department of Medicine/Center of Hematology at Karolinska Institute, Stockholm, Sweden.
⁹ Service d'Hématologie, Centre Léon Bérard, Lyon, France.
¹⁰ Hematology Department, Hospital de laSanta Creu i Sant Pau, Barcelona, Spain.
¹¹ Department of Hematology, Copernicus Memorial Hospital, Medical University of Lodz, Lodz, Poland.
¹² Department Medicine III, University of Ulm, Ulm, Germany; and.
¹³ Department of Hematology, Hospital Clínic, University of Barcelona, Barcelona, Spain.

PMID: 29997221
DOI: 10.1182/blood-2018-01-826008

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.

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

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

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