Earlier this week the U.S. News and World Report released their annual survey of “Best Hospitals”. NewYork Presbyterian one of the country’s largest and most comprehensive hospitals was ranked New York’s No. 1 hospital for the 16th year in a row, and No. 6 ranked hospital in all of the United States. Dr. Augustine M.K. Choi, interim dean of Weill Cornell Medicine commented,
“Our esteemed physicians and scientists at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medicine always put patients first, providing them with the finest, most comprehensive care so that they can live their healthiest lives. Together we create one of the top academic medical centers in the United States, motivated by a shared commitment: to drive excellence in healthcare and truly make a difference in New York and beyond.”
This commitment is shared by the physicians, researchers, and staff in the Lymphoma Program.
The Fast Track Designation was introduced by the FDA in 1997 under the FDA Modernization Act. It was designed to speed up the development and review of drugs that treat serious conditions and fill an unmet medical need. Like all expedited designations, the Fast Track was designed to get new treatments into the hands of patients in need.
The Fast Track designation must be requested by the treatment’s sponsor. To determine whether a treatment warrants a Fast Track designation the FDA decides whether a drug shows promise in treating a serious condition or fills an unmet medical need. Determining whether a drug treats a condition that is “serious” is largely a subjective matter, but cancers including lymphoma are universally agreed upon to match the criteria of serious conditions. The factors the FDA will consider include the drug’s impact on survival, day-to-day functioning, and if left untreated, whether a less severe condition will turn into a more serious condition. An unmet medical need provides a treatment option to patients where no such option previously existed.
If other treatment options are already available then the treatment applying for the Fast Track designation must show superior effectiveness, avoid any major side effects found in currently available therapies, improve upon the diagnosis to show an improved outcome, or address an emerging or anticipated public health need.
Treatments that meet these criteria are eligible for more support from the FDA for their application process. If the relevant criteria is met they are also eligible for the accelerated approval and priority review designations.
Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma in adults. While DLBCL is potentially curable, patients with relapsed or refractory DLBCL cannot be cured with chemotherapy due to the aggressive nature of their disease and their tumors lack of response to chemotherapy. Therefore treating this subset of DLBCL patients requires new treatment options. Recently researchers from Dr. Leandro Cerchietti’s lab published a paper on a potential new target for DLBCL.
DLBCL tumor cells grow because malignant cancer cells disturb cell processes like DNA methylation and histone acetylation that are two key parts of the “epigenomic” machinery. Researchers in Dr. Leandro Cerchietti’s lab have previously reported that inhibiting one of these epigenomic pathways by using DNA methyltransferase inhibitors (DNMTI), makes tumors more susceptible to chemotherapy treatments. His group hypothesized that inhibiting both epigenomic pathways by combining DNMTI with a histone deacetylase inhibitor (HDI) could be a potential treatment option for DLBCL patients that relapsed after chemotherapy or never responded to chemotherapy.
Leandro Cerchietti, MD
Researchers decided to evaluate the effectiveness of combining the HDI, vorinost with the DNMTI’s, azacitidine or decitabine in pre-clinical models to determine the feasibility of beginning phase I human trials. Researchers found no significant toxicity increase in initial laboratory and animal trials. In the ensuing trial 18 patients with a median of 3 prior therapies were treated with 4 different dose levels of azacitidine and vorinostat. The most common side effects were manageable and included hematological, gastrointestinal, and metabolic toxicities.
The clinical benefit to the combined epigenetic treatment was low as only one patient experienced a partial response. However, 2 of the 7 patients, who received chemotherapy after the study achieved a complete response, while 3 others patients derived a significant clinical benefit. This suggests that the proposed epigenetic combination could make tumors more susceptible to chemotherapy treatments.
Further research in pre-clinical models confirmed that DNMTI is the most important drugs in the combination to achieve chemosensitization, which makes tumors more susceptible to chemotherapy treatment. The data supports the strategy of using DNMTI in relapsed and refractory DLBCL patients to overcome disease resistance and improve their outcomes. This treatment could potentially be a new option for patients with relapsed or refractory DLBCL.
New Developments in Lymphoma 