TY - JOUR
T1 - High-risk chronic lymphocytic leukemia in the era of pathway inhibitors: Integrating molecular and cellular therapies
AU - Dreger, P
AU - Ghia, P
AU - Schetelig, J
AU - Van Gelder, M
AU - Kimby, E
AU - Michallet, M
AU - Moreno, C
AU - Robak, T
AU - Stilgenbauer, S
AU - Montserrat, E
AU - (ERIC), on behalf of the European Research Initiative on CLL
AU - Blood, the European Society for
AU - (EBMT), Marrow Transplantation
PY - 2018
Y1 - 2018
N2 - 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.
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.
U2 - 10.1182/blood-2018-01-826008
DO - 10.1182/blood-2018-01-826008
M3 - Article
VL - 132
SP - 892
EP - 902
JO - Blood
JF - Blood
SN - 0006-4971
IS - 9
ER -