Last week Weill Cornell researcher Dr. Ari Melnick sat down with Targeted Oncology to briefly summarize the potential of EZH2 in treating diffuse large B-cell lymphoma.
FDA Approves Ibrutinib for Chronic Lymphocytic Leukemia
Last week the FDA announced the approval of ibrutinib for patients with chronic lymphocytic leukemia. According to their press release:
“The U.S. Food and Drug Administration today expanded the approved use of Imbruvica (ibrutinib) for chronic lymphocytic leukemia (CLL) patients who have received at least one previous therapy.”
“CLL is a rare blood and bone marrow disease that usually gets worse slowly over time, causing a gradual increase in white blood cells called B lymphocytes, or B cells. The National Cancer Institute estimates that 15,680 Americans were diagnosed and 4,580 died from the disease in 2013.”
“Imbruvica works by blocking the enzyme that allows cancer cells to grow and divide. In November 2013, the FDA granted Imbruvica accelerated approval to treat patients with mantle cell lymphoma, a rare and aggressive type of blood cancer, if those patients received at least one prior therapy.”
“Today’s approval provides an important new treatment option for CLL patients whose cancer has progressed despite having undergone previous therapy,” 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 FDA completed its review of Imbruvica’s new indication under the agency’s accelerated approval process, which played a vital role in rapidly making this new therapy available to those who need it most.”
The full press release can be read on their website.
The full listing of CLL trials at WCMC is available on the clinical trials website. Look to this space for further news concerning ibrutinib trials for CLL patients at WCMC.
Two Modes of DLBCL Relapse
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.
New Developments in Lymphoma 