Kinetics of CLL cells in tissues and blood during therapy with the BTK inhibitor ibrutinib.
The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has excellent clinical activity in patients with chronic lymphocytic leukemia (CLL). Characteristically, ibrutinib causes CLL cell redistribution from tissue sites into the peripheral blood during the initial weeks of therapy. To better characterize the dynamics of this redistribution phenomenon, we correlated serial lymphocyte counts with volumetric changes in lymph node and spleen sizes during ibrutinib therapy. Kinetic parameters were estimated by applying a mathematical model to the data. We found that during ibrutinib therapy, 1.7% ± 1.1% of blood CLL cells and 2.7% ± 0.99% of tissue CLL cells die per day. The fraction of the tissue CLL cells that was redistributed into the blood during therapy was estimated to be 23.3% ± 17% of the total tissue disease burden. These data indicate that the reduction of tissue disease burden by ibrutinib is due more to CLL cell death and less to egress from nodal compartments.
Departments of Mathematics and Ecology and Evolutionary Biology, University of California, Irvine, CA;
Dominik
D
Wodarz
Department of Diagnostic Radiology and.
Naveen
N
Garg
Departments of Mathematics and Ecology and Evolutionary Biology, University of California, Irvine, CA;
Natalia L
NL
Komarova
Department of Leukemia, MD Anderson Cancer Center, Houston, TX; and.
Ohad
O
Benjamini
Department of Leukemia, MD Anderson Cancer Center, Houston, TX; and.
Michael J
MJ
Keating
Department of Leukemia, MD Anderson Cancer Center, Houston, TX; and.
William G
WG
Wierda
Department of Leukemia, MD Anderson Cancer Center, Houston, TX; and.
Hagop
H
Kantarjian
Pharmacyclics Inc., Sunnyvale, CA.
Danelle
D
James
Department of Leukemia, MD Anderson Cancer Center, Houston, TX; and.
Susan
S
O'Brien
Department of Leukemia, MD Anderson Cancer Center, Houston, TX; and.
Jan A
JA
Burger
D000225:Adenine / Q000031:analogs & derivatives; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology; D010880:Piperidines; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*
D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D000225:Adenine