Author: lymphomaprogram

Located on the Upper East Side of New York City, the Lymphoma Program at Weill Cornell Medical College/NewYork Presbyterian Hospital is internationally recognized for our efforts to enable patients with non-Hodgkin lymphoma, Hodgkin disease and related disorders to have the best possible clinical outcome, including cure when possible.

Two Modes of DLBCL Relapse

Yanwen JiangBy Yanwen Jiang PhD 

Despite improvements in care for patients with diffuse large B-cell lymphoma (DLBCL), roughly one-third of patients do not respond to initial therapy or relapse within the first 2-3 years after treatment. Unfortunately, our current understanding of the molecular mechanisms of relapse is extremely poor.

During the recent 2013 American Society of Hematology meeting, we reported for the first time that there exist at least two distinct scenarios of DLBCL relapse.  In the first scenario, the tumor cells at diagnosis are almost genetically identical to tumor cells at relapse. Both tumors harbor the same set of mutations with the relapsed tumor possessing a few additional mutations, suggesting that the relapsed tumor evolved continuously from the tumor present at diagnosis. We termed this scenario “linear” mode.  In the second scenario, the tumors at diagnosis and relapse carry different mutations, suggesting that an early divergent event occurred and that the tumors developed in parallel.  Therefore, we named this scenario the “divergent” mode.  Moreover, we observed that tumors with higher genetic heterogeneity at diagnosis were more likely to relapse through the divergent mode. This may provide a foundation for evaluation of different treatment strategies for different relapse modes.

Currently, we are expanding our study to investigate the role of epigenetics, particularly DNA methylation, in DLBCL relapse.  For more research information on DLBCL, and relapsed DLBCL, please visit our websites at the Elemento Lab and the Melnick lab.

EZH2 Represents a New Target for Treatment of B-cell Lymphomas

wendybeguelinBy Wendy Béguelin, PhD

Chemotherapy for diffuse large B-cell lymphomas can have side effects and is not always effective. By targeting proteins that drive and define the lymphoma, it may be possible to reduce  our reliance on chemotherapy. Most B-cell lymphomas arise from a structure called the “germinal center” in lymph nodes. During the normal immune response, B-cells from germinal centers express high levels of proteins called BCL6 and EZH2. The combined and coordinated action of BCL6 and EZH2 can induce specific genetic changes that result in the development of malignant lymphomas. Our research, presented as 1 of 6 papers chosen from over 6,000 during the plenary session of the recent 2013 American Society of Hematology, suggests that combinations of BCL6 and EZH2 inhibitors are highly effective in destroying lymphomas and thus represent an exciting new, rationally designed treatment regimen. Fortunately, EZH2 inhibitors are already in phase I clinical trials, and specific and effective BCL6 inhibitors will be going into clinical trials.

In the Melnick Lab at Weill Cornell Medical College we are working with colleagues to develop new strategies to eradicate lymphoma and improve patient care. Please look to this space for further updates on lymphoma research in the Lymphoma Program at Weill Cornell. 

Ibrutinib Receives FDA Approval for MCL Therapy

Yesterday, the FDA announced approval for ibrutinib, or Imbruvica in the treatment of patients with mantle cell lymphoma (MCL), who have previously received at least one other therapy. According to the FDA press release:

“Imbruvica is intended for patients with MCL who have received at least one prior therapy. It works by inhibiting the enzyme needed by the cancer to multiply and spread. Imbruvica is the third drug approved to treat MCL. Velcade (2006) and Revlimid (2013) are also approved to treat the disease.”

“Imbruvica’s approval demonstrates the FDA’s commitment to making treatments available to patients with rare diseases,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “The agency worked cooperatively with the companies to expedite the drug’s development, review and approval, reflecting the promise of the Breakthrough Therapy Designation program.”

“Imbruvica is the second drug with breakthrough therapy designation to receive FDA approval. The Food and Drug Administration Safety and Innovation Act, passed in July 2012, gave the FDA the ability to designate a drug a breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases.”

“The FDA is approving Imbruvica under the agency’s accelerated approval program, which allows the FDA to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials. The FDA also granted Imbruvica priority review and orphan-product designation because the drug demonstrated the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition and is intended to treat a rare disease, respectively.”

The physicians in the Lymphoma Program at Weill Cornell Medical College are happy to have had the opportunity to be part of this important study, and would like to thank all the patients who participated in the trials. Further information on  trials involving MCL and/or ibrutinib can be found on our listings of non-Hodgkin lymphoma clinical trials.