Diffuse Large B-Cell Lymphoma Responds to Ibrutinib

Diffuse Large B-Cell Lymphoma Responds to Ibrutinib

July 27, 2015

A new study finds an aggressive form of lymphoma responds to ibrutinib (Imbruvica), which targets the B-cell receptor. This was first reported in the July 20, 2015 online edition of Nature Medicine.

A new study finds an aggressive form of lymphoma responds to ibrutinib (Imbruvica), which targets the B-cell receptor. This was first reported in the July 20, 2015 online edition of Nature Medicine.1

The clinical trial was jointly conducted by the National Cancer Institute (NCI) and Pharmacyclics, Sunnyvale, California. The trial included 80 patients diagnosed with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) with variations in mutations. The study demonstrated that ibrutinib produced complete or partial responses in 37% of those with activated B-cell-like (ABC) DLBCL, but in only 5% of patients with a subtype of DLBCL, called germinal center B-cell-like (GCB).

A little more than half of the patients with ABC tumors with B-cell receptor (BCR) mutations responded to ibrutinib (55.5%), especially those with concomitant myeloid differentiation primary response 88 (MYD88) mutations (80%). However, the highest number of responses occurred in ABC tumors that lacked BCR mutations (31%). This result suggests that oncogenic BCR signaling in ABC does not require BCR mutations.

“This is the first clinical study to demonstrate the importance of precision medicine in lymphomas,” said  co-leader Wyndham Wilson, MD, PhD, NCI Center for Cancer Research in a National Institutes of Health (NIH) press release.2 The discovery of the lymphoma subtypes suggest that targeted treatments could be developed for each subtype.

The target for ibrutinib is an enzyme called Bruton’s tyrosine kinase (BTK). BTK is a major player in B-cell receptor signaling. This study provides clinical evidence that ABC, but not GBC tumors, may produce abnormal B-cell receptor signals that promote the survival of cancer cells by activating BTK.

Lymphomas occur when there is an abnormal growth of white blood cells. DLBCL originates from B cells, which are responsible for the way the immune system responds to attackers. DLBCL is a particularly aggressive form of lymphoma, yet has a high cure rate, depending on the age and health of the patient upon diagnosis. With this better understanding of lymphoma subtypes, more precise cancer care is within reach.

 

 

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