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.

Weill Cornell Researchers Unlock Potential New Target for Relapsed/Refractory DLBCL

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
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.

The FDA Priority Review Designation: A Primer

Picture1By Peter Martin, M.D.

Under the Prescription Drug User Act the FDA created a two-tiered system for review of new drug applications (NDA). The first tier of this system, known as Standard Review, is for treatments that offer a minor improvement over existing therapies, and sets the timeline to review at 10 months from receiving the NDA. The second tier, the Priority Review, is for drugs that offer major advances over existing therapies, or provide a treatment where none had previously existed, and reduces the approval timeframe of review to 6 months.

Significant improvements over pre-existing treatments include evidence of increased effectiveness in treatment, prevention, or diagnosis, reduction in treatment-limiting reactions, evidence of safety and effectiveness in a new patient population, and documented enhancement of patient compliance that is thought to lead to an improvement in serious outcomes.

Unlike other expedited approval programs with different levels of standards the Priority Review designation does not change the scientific or medical standards used for approval by the FDA. Instead more resources are devoted to expediting approval for the treatments that receive this designation because the FDA has decided chosen treatments serve a much greater need. To receive the Priority Review designation the FDA requires evidence of increased effectiveness in treatment prevention, or diagnosis of a condition.

Previous Entries in the Primer Series

The FDA Approval Process
The FDA Breakthrough Therapy Designation
THE FDA Accelerated Approval Designation

Dr. John Allan Describes a Clinical Trial for Patients with B-Cell Malignancies

In this video Dr. John Allan describes the benefits of a recently opened clinical trial for men and women with CD20+ B-cell malignancies, including B-NHL and CLL.

If you’re interested in participating in this trial please call 212-746-2919 for more information. A full listing of B-cell malignancy trials at Weill Cornell Medicine can be found on the Joint Clinical Trials website.