Weill Cornell Breakthrough Research: Shutting Down DLBCL Master Protein; Potential for New Treatments

Reporting in Nature Immunology, Weill Cornell’s Dr. Ari Melnick and his research team have reported an important research breakthrough in diffuse large-B cell lymphoma (DLBCL) that may offer hope for new treatments for aggressive lymphomas.

Dr. Melnick has found that it is possible to shut down the protein Bcl6, a powerful master regulatory transcription factor that is the key to survival for many aggressive lymphomas arising from the B-cells.

“The finding comes as a very welcome surprise,” says the study’s lead investigator, Dr. Ari Melnick, Gebroe Family Professor of Hematology/Oncology and director of the Raymond and Beverly Sackler Center for Biomedical and Physical Sciences at Weill Cornell.

The protein Bcl6 was previously considered too complex to target with individual drugs, because of its centrality in the functioning of the body’s healthy immune cells.

“This means the drugs we have developed against Bcl6 are more likely to be significantly less toxic and safer for patients with this cancer than we realized,” says Dr. Melnick.

DLBCL is the most common subtype of non-Hodgkin lymphoma — the seventh most frequently diagnosed cancer, with many patients resistant to currently available treatments. Presently, there are ongoing clinical trials for those suffering from non-Hodgkin’s lymphoma and other forms of lymphoma at the Weill Cornell Lymphoma Center.

The full press release can be read here.

ASCO Update: Lenalidomide + Rituximab Superior to Lenalidomide Alone in Relapsed Lymphoma

John Leonard, MD

At the recent meeting of the American Society of Clinical Oncology (ASCO), Dr. John Leonard, the director of the Weill Cornell Lymphoma Program, presented the results of the CALGB 50401 trial. The trial compared lenalidomide plus rituximab versus lenalidomide alone in 94 patients with previously treated follicular lymphoma.

Although significant side effects were similar in both treatment arms, the patients treated with the lenalidomide plus rituximab were more likely to respond to treatment (75% vs. 49%) and remain on treatment compared to lenalidomide alone. Based on these results, the investigators concluded that the lenalidomide-rituximab regimen should be considered as a platform for addition of new drugs in future studies.

Click here to read the published abstract.

ASCO Update:Bendamustine plus rituximab beats CHOP plus rituximab as first-line treatment for indolent and mantle cell lymphoma

By Peter Martin, MD

At the plenary session of the American Society of Clinical Oncology (ASCO) on Sunday, June 3, Dr. Mattias Rummel from Germany presented updated results from a phase 3 trial initially presented at the American Society of Hematology (ASH) in 2009. The study compared bendamustine plus rituximab (BR) to CHOP chemotherapy plus rituximab (R-CHOP) in over 500 patients with indolent and mantle cell lymphoma.

Now with a median follow-up period of 45 months, the updated data were consistent with the previously reported findings. Bendamustine plus rituximab (BR) was better tolerated than R-CHOP, with significantly less neutropenia, fewer infections, and no alopecia (hair loss), and was also more effective, reducing the risk of progression roughly two-fold.

Importantly, there was no difference in the rate of transformation to aggressive lymphoma, the rate of secondary malignancies, and the ability to collect stem cells. These data support the design of ongoing and planned cooperative group trials further evaluating the first-line use of BR and BR-based combinations.

In his discussion of the abstract, Dr. Michael Williams from the University of Virginia agreed that the data were promising but cautioned that a peer-reviewed publication of the data remains to be seen.

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