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Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy by Jennifer A. Woyach, Kelly Smucker, Lisa L. Smith, Arletta Lozanski, Yiming Zhong, Amy S. Ruppert, David Lucas, Katie Williams, Weiqiang Zhao, Laura Rassenti, Emanuela Ghia, Thomas J. Kipps, Rose Mantel, Jeffrey Jones, Joseph Flynn, Kami Maddocks, Susan O’Brien, Richard R. Furman, Danelle F. James, Fong Clow, Gerard Lozanski, Amy J. Johnson, and John C. Byrd Blood Volume 123(12):1810-1817 March 20, 2014 ©2014 by American Society of Hematology

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Page 1: Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy

Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and

does not indicate a suboptimal response to therapy

by Jennifer A. Woyach, Kelly Smucker, Lisa L. Smith, Arletta Lozanski, Yiming Zhong, Amy S. Ruppert, David Lucas, Katie Williams, Weiqiang Zhao, Laura

Rassenti, Emanuela Ghia, Thomas J. Kipps, Rose Mantel, Jeffrey Jones, Joseph Flynn, Kami Maddocks, Susan O’Brien, Richard R. Furman, Danelle F. James, Fong

Clow, Gerard Lozanski, Amy J. Johnson, and John C. Byrd

BloodVolume 123(12):1810-1817

March 20, 2014

©2014 by American Society of Hematology

Page 2: Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy

Protein and gene expression of BCR signaling components in persistent lymphocytes compared with baseline.

Jennifer A. Woyach et al. Blood 2014;123:1810-1817

©2014 by American Society of Hematology

Page 3: Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy

Nuclear and cytoplasmic localization of BTK, ERK, and AKT in persistent lymphocytes following ibrutinib therapy and ability of persistent lymphocytes to stimulate.

Jennifer A. Woyach et al. Blood 2014;123:1810-1817

©2014 by American Society of Hematology

Page 4: Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy

Real-time PCR of BCR pathway–associated genes in persistent lymphocytes.

Jennifer A. Woyach et al. Blood 2014;123:1810-1817

©2014 by American Society of Hematology

Page 5: Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy

Persistent lymphocytes are not addicted to a single signaling pathway.

Jennifer A. Woyach et al. Blood 2014;123:1810-1817

©2014 by American Society of Hematology

Page 6: Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy

PFS of patients with persistent lymphocytosis is not inferior to those achieving complete or PR by 12 months.

Jennifer A. Woyach et al. Blood 2014;123:1810-1817

©2014 by American Society of Hematology


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