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B-Cell Receptor Inhibitor Response Criteria in CLL

Insights From:Jennifer R. Brown, MD, PhD, Harvard Medical School; Richard R. Furman, MD, Weill Cornell Medical College; Brad S. Kahl, MD, UW Carbone Cancer Cente
Published: Thursday, Sep 10, 2015

 
Traditionally, a response in chronic lymphocytic leukemia (CLL) was defined by a decline in white blood cell counts; however, the type of response seen with B-cell receptor (BCR) pathway inhibitors has altered this definition. In early phase I studies, patients treated with BCR inhibitors, such as ibrutinib, reported feeling better almost immediately and had shrinkage of their lymph nodes, but these events were coupled with a simultaneous rise in white blood cell levels, explains Jennifer Brown, MD, PhD.

During its early development, BCR inhibitor therapy was discontinued due to the fear that the increase in white blood cells represented progressive disease, says Brown. Today, it is thought that this rise is likely due to redistribution of cells from niche sites, including lymph nodes and bone marrow, into peripheral blood where they die at a somewhat enhanced rate because they are not receiving support from their initial microenvironment, explains Brown.

As a result of this phenomenon, the response criteria for CLL were modified for individuals treated with BCR inhibitors. The criteria for response are now based on nodule disease, with a new category for partial response with lymphocytosis, for individuals who have at least a 50% reduction in nodule burden, yet have a lymphocyte count that is above a normal 50% reduction from baseline.
 
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Traditionally, a response in chronic lymphocytic leukemia (CLL) was defined by a decline in white blood cell counts; however, the type of response seen with B-cell receptor (BCR) pathway inhibitors has altered this definition. In early phase I studies, patients treated with BCR inhibitors, such as ibrutinib, reported feeling better almost immediately and had shrinkage of their lymph nodes, but these events were coupled with a simultaneous rise in white blood cell levels, explains Jennifer Brown, MD, PhD.

During its early development, BCR inhibitor therapy was discontinued due to the fear that the increase in white blood cells represented progressive disease, says Brown. Today, it is thought that this rise is likely due to redistribution of cells from niche sites, including lymph nodes and bone marrow, into peripheral blood where they die at a somewhat enhanced rate because they are not receiving support from their initial microenvironment, explains Brown.

As a result of this phenomenon, the response criteria for CLL were modified for individuals treated with BCR inhibitors. The criteria for response are now based on nodule disease, with a new category for partial response with lymphocytosis, for individuals who have at least a 50% reduction in nodule burden, yet have a lymphocyte count that is above a normal 50% reduction from baseline.
 
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