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 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 tumours will die when this pathway is inhibited.

In collaboration with Dr. Lou Staudt, Pharmacyclics and associate investigators, a clinical trial of a very potent inhibitor of Bruton Tyrosine Kinase (BTK) called ibrutinib was performed. Inhibition of BTK by ibrutinib blocks the abnormal BCR signaling in ABC DLBCL tumour cells and kills them.

In a clinical trial presented by my colleague at this EHA meeting, we show that ibrutinib significantly kills tumours in patients with ABC DLBCL. For the first time it was shown that tumours 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.

Source: EHA