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Blood Cancers Video Library: Are All DLBCL Made Equally?

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GRACE joined a number of top faculty in the area of hematology in Whistler BC, for the 3rd Annual Summit on Hematologic Malignancies.  Wyndham Wilson, MD, PhD, Senior Scientist at NIH, Director Lymphoid Tumor Group, Senior Investigator Lymphoid Malignancies Branch of the National Cancer Institute talks with GRACE about the differences between all DLBCL, (Diffuse Large B-Cell Lymphoma) and their various tumor types which now take their names from the cell of origin from which they come.

 

 

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Chronic Lymphocytic Leukemia

and Non-Hodgkin Lymphoma

Are all DLBCL Made Equally?

Wyndham Wilson, MD, PhD

Senior Scientist at NIH, Director Lymphoid Tumor Group

Senior Investigator, Lymphoid Malignancies Branch of the National Cancer Institute

 

I first want to talk about the diffuse large cell lymphoma, which actually constitutes the most common type of lymphoma, comprising approximately 30 percent of all lymphomas. For many years we used to think this was a single tumor type, but it had also been known for many years that it really had a very wide natural history and some people were readily cured with chemotherapy and others not. Around 15 years ago, using one of the first studies to look at what’s called gene expression profiling, it was shown that large cell is actually not a single tumor type but is actually made up of multiple tumor types. These various tumor types now take their names from the cell of origin from which they come. Two of the major types are called the germinal center type, which is a tumor that comes from a cell that’s part of the normal germinal center, and the other largest group comes from what is called an activated B-cell, which comes from a lymphocyte that has gone through the germinal center.

Now that we know that there are multiple different types, there has also been much research to try to understand what the various causes of these tumors are. What we now know is that the so-called ABC types, or the activated B-cell types are driven by activation of a transcription factor called NF-kB. But what really became clear over the last five to six years is that this transcription factor NF-kB is really being driven by what we call B-cell receptor signaling. About five or six years ago a drug, which is a protein kinase inhibitor, began to be tested. This protein kinase inhibitor inhibited a key kinase within the B-cell receptor signaling cascade called Bruton’s tyrosine kinase. The drug, which has now been approved for multiple lymphomas, is called ibrutinib, and it really has transformed the treatment of multiple lymphoma subtypes.

We recently did a study of this drug in relapsed ABC large cell, and we actually found that even in that very difficult to treat disease that approximately 40 percent of cases had at least a 50 percent shrinkage with that drug. A result of this study was that a large randomized study has now actually been started, and even has been finished, called the PHOENIX study, and this is a randomized study of R-CHOP, which is standard therapy for large cell lymphoma, with one arm being the control arm where they just get standard therapy and the other arm being R-CHOP plus this new drug. We are hoping that is a positive trial, it completed accrual last year, and we expect results from that trial over the next two to three years.

The other major type of large cell is the so-called germinal center large cell and that tumor type is primarily driven by what’s called the BCL6 transcription factor. Many people have tried to make drugs that actually inhibit that. We’ve yet to have one, but there are some other strategies that are on the horizon that may be useful for this type as well. The good news about the germinal center type is that it tends to be more sensitive to chemotherapy, and the cure rate with standard regimens such as R-CHOP as well as a newer regimen called Dose Adjusted EPOCH-R, have ranged anywhere between 70 and 90 percent. So we do have very good therapy for that. 

 

 

 

 


 

 

 


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