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Novel Regimens Explored for Rare DLBCL Subtypes

Gina Columbus @ginacolumbusonc
Published: Wednesday, Jun 14, 2017

Sarah Rutherford, MD.

Sarah Rutherford, MD.

For patients with diffuse large B-cell lymphoma (DLBCL) who have more aggressive disease and are less likely to respond to chemotherapy, it is possible that they may have 2 of the rarer DLBCL subtypes that require different treatments, according to Sarah Rutherford, MD.

The subtypes—double-hit lymphomas and double-protein expressor lymphomas—are in 5% to 10% of all patients with DLBCL. Currently, an ongoing, multicenter phase I clinical trial is exploring a novel regimen of venetoclax (Venclexta) plus dose-adjusted EPOCH-R in patients with these lymphomas who harbor translocations in MYC, BCL-2, or BCL-6 (NCT03036904).

Rutherford, an assistant professor of medicine, Weill Cornell Medicine/New York-Presbyterian Hospital, discussed these rare DLBCL subtypes, ongoing research to improve outcomes for these patient populations, and the potential role of chimeric antigen receptor (CAR) T-cell therapy during an interview at the 2017 OncLive® State of the Science SummitTM on Hematologic Malignancies.

OncLive: Please provide an overview of your presentation on DLBCL.

Rutherford: I focused on the most aggressive cases of DLBCL, which are called double-hit lymphomas. Then, there is another category called double-protein expressor lymphomas. My focus and research is with these more difficult-to-treat diseases and coming up with novel strategies to try to improve the cure rates. 

First, I went over the diagnoses and the current treatment strategies. I talked about some of the clinical trials that we have opened and some other exciting treatments that we have planned for the future. 

Can you discuss the features of each of these subtypes and highlight the prevalence of them?

As a background, DLBCL is the most common type of non-Hodgkin lymphoma and also the most common type, overall, of lymphoma. It is an aggressive disease that is usually cured in about two-thirds of patients using R-CHOP. For that other one-third of patients who are not cured, there have been strategies over the last 10 years or so to try and figure out what is different about those patients and what can we do to get them cured, as well. 

Some chromosome changes that can occur in some of these patients with lymphoma, causing these people to have more aggressive disease, make it not as responsive to chemotherapy. The 2 chromosome changes are called MYC and BCL-2. There is another one called BCL-6 that can also be involved. When 2 of those are rearranged, they are called double-hit lymphomas.

Then, the other category that is talked about is double-protein expressor lymphomas. Those are the same as MYC and BCL-2, but they are not rearranged; they have an increased expression of them. They are not quite as difficult to cure as the double-hit lymphomas, but they also are more aggressive disease. 

How are these rarer lymphomas currently treated and what novel strategies are being explored?

The standard treatment for DLBCL is R-CHOP. It is given for 6 treatments over about 4.5 months. That is the standard for DLBCL. For these double-hit lymphomas, based on a bunch of retrospective studies, there really isn’t a prospective study that has looked specifically at that patient population. It makes up about 5% to 10% of patients with DLBCL—so fairly small numbers there. 

The data suggest that giving more intense treatment rather than R-CHOP is often used, which is dose-adjusted EPOCH-R. It is given usually in the hospital over 5 days and is called an infusional chemotherapy. It is given continuously over that time period. At this point, that is what we use at Weill Cornell Medicine and at many other academic institutions. Many hospitals throughout the country are using that regimen. 

We are using it as a backbone to study investigational drugs for clinical trials. Right now, our hospital, along with several other institutions in the country, is running a clinical trial of dose-adjusted EPOCH-R plus venetoclax. This is a BCL-2 inhibitor and is a targeted oral drug, which is FDA approved for a couple of other diseases, such as chronic lymphocytic leukemia. We are combining it with the dose-adjusted EPOCH-R in all patients with DLBCL who meet the criteria in order to find the dose that is best tolerated with this chemotherapy regimen.




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