Targeting the B-cell Receptor in Aggressive B-cell Lymphomas

STOCKHOLM, June 14, 2013 /PRNewswire/ --

Dr Wyndham Wilson will give an update on recent developments in the treatment of lymphomas with small molecules.

The last 30 years have seen a plethora of treatments for diffuse large B-cell lymphoma (DLBCL) but few advances have been made. Recent studies have identified B-cell receptor signaling as critical for many B-cell lymphomas including the most common type, called diffuse large B-cell lymphoma (DLBCL). Recent studies have shown that DLBCL is actually not a single disease but at least 3 different diseases, each with its own critical abnormalities that allow it to survive as a malignancy.  The most difficult to treat type of DLBCL is called the Activated B-cell (ABC) subtype, which is dependent on abnormal signaling of the B-cell receptor (BCR). Work by Dr. Lou Staudt has shown that these tumors will die when this pathway is inhibited.

In collaboration with Dr. Lou Staudt, Pharmacyclics and associate investigators, we performed a clinical trial of a very potent inhibitor of Bruton Tyrosine Kinase (BTK) called ibrutinib.  Inhibition of BTK by ibrutinib blocks the abnormal BCR signaling in ABC DLBCL tumor cells and kills them.  In a clinical trial presented by my colleague at this EHA meeting, we show that ibrutinib significantly kills tumors in patients with ABC DLBCL. Importantly, we show for the first time that tumors that harbor specific abnormalities in the BCR signaling are the most sensitive to ibrutinib. This proof of principal trial will help investigators identify those patients most likely to benefit from this drug.

Presenter : Wyndham H. Wilson

Affiliation : National Cancer Institute, USA

Topic: THE BRUTON'S TYROSINE KINASE (BTK) INHIBITOR, IBRUTINIB (PCI-32765), HAS PREFERENTIAL ACTIVITY IN THE ACTIVATED B CELL-LIKE (ABC) SUBTYPE OF RELAPSED/REFRACTORY (R/R) DLBCL: INTERIM PHASE 2 RESULTS (abstract number S1180)

About the EHA Annual Congress

Hematology is a specialty that covers everything to do with blood: its origin in the bone marrow, diseases of blood and their treatments. The latest data on research and developments will be presented. The topics range from stem cell physiology and development, to leukemia, lymphoma, myeloma - diagnosis and treatment; red blood cells -, white blood cells- and platelet disorders; thrombosis and bleeding disorders.