Dose-Adjusted EPOCH-Rituximab Shows Encouraging Results for Patients with Primary Mediastinal B-Cell LymphomaPosted: April 18, 2013
Initially recognized in the 1980s, primary mediastinal B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL) arising in the thymus. Representing less than 3% of non-Hodgkin lymphoma cases, PMBCL has a skewed age distribution affecting young adults, especially young women. Historically, patients with PMBCL have been treated with mediastinal radiation following chemotherapy based on evidence that chemotherapy alone was insufficient. Despite the high cure rates with this strategy, mediastinal radiation in young patients can be associated with late adverse effects, including premature cardiovascular disease and secondary cancers.
Researchers from the National Cancer Institute (NCI) and their partner institutions recently completed a phase II study of infusional dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (DA-EPOCH-R) with no mediastinal radiation complement. In 51 patients with a median age of 30 years, of which 59% were women, the overall survival rate was 97% at the median 5-year follow-up. From these results, researchers suggested that DA-EPOCH-R therapy obviated the need for radiotherapy in patients with PMBCL.
While these results from this phase II study are encouraging, they will need to be confirmed with further research.
Weill Cornell Breakthrough Research: Shutting Down DLBCL Master Protein; Potential for New TreatmentsPosted: March 4, 2013
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 Bc16, 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 Bc16 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.
At the 16th Annual International Congress on Hematologic Malignancies, Dr. John Leonard, the director of the Lymphoma Program at Weill Cornell Medical College, discussed several novel therapies currently under investigation for DLBCL. Today OncLive published an article, “Beyond R-CHOP-21: What’s New in Diffuse Large B-Cell Lymphoma” summarizing Dr. Leonard’s discussion.
“The current standard for patients with advanced diffuse large B-cell lymphoma (DLBCL) is R-CHOP-21 (21-day rituximab-cyclophosphamidedoxorubicin- vincristine-prednisone). However, while this regimen cures approximately two-thirds of patients, a significant fraction of patients will still relapse, and the prognosis for these patients is poor.”
Approaches being evaluated include substituting an alternate chemotherapy regimen for CHOP in combination with rituximab; R-EPOCH (rituximabetoposide- prednisone-vincristine-doxorubicin-cyclophosphamide); and adding a new agent to R-CHOP-21.
Click here to read the full article in in OncLive.
Dr. John Leonard, Director of the Weill Cornell Lymphoma Program, was on the panel of experts participating in Cancer Care’s Connect Education Workshop, “Update on Diffuse Large B-Cell Lymphoma” on October 5.
Click the player below to listen to the workshop, or click here to download the discussion on the Cancer Care website.
Weill Cornell’s Dr. John Leonard will be on the panel of experts participating in Cancer Care’s telephone workshop “Update on Diffuse Large B-Cell Lymphoma” on Wednesday, October 5 from 1:30 to 2:30 pm, Eastern Time.
The workshop is free of charge. No phone charges apply. However, pre-registration is required to secure a place on the call. Click here for more information and to register for the workshop.
Lymphoma in the News: Two Important Studies Take Us One Step Closer to Personalized Lymphoma TherapyPosted: September 26, 2011
Based on multiple randomized phase 3 studies initiated over a decade ago, R-CHOP chemotherapy is the standard of care for first-line treatment of patients with diffuse large B-cell lymphoma (DLBCL). However, sometimes R-CHOP is not successful. Fortunately, our understanding of lymphoma has evolved over the past decade.
It is increasingly clear that “DLBCL” is a heterogeneous group of related tumors. Studies using gene expression profiling , have revealed that DLBCL can be divided into three subgroups based on the probable cell of origin (i.e., the cell from which the lymphoma was derived): activated B-cell like DLBCL (ABC), germinal center-like DLBCL (GCB), and a third group, termed “type 3”, that doesn’t possess any specific characteristics (click here to read the abstract). So far, the clinical relevance of differentiating between the ABC and GCB subtypes of DLBCL remains somewhat unclear. Nonetheless, studies done at Weill Cornell Medical College and elsewhere have suggested that certain treatments might preferentially benefit one subtype (see here and here). As a result, ongoing clinical trials are evaluating newer therapies targeted to the appropriate subgroup.
Just as we are beginning to understand the significance of DLBCL gene expression profiles, recent technological advances in DNA sequencing are making the rapid, high-resolution sequencing of a tumor’s entire genome (DNA code) possible and affordable . Two recently published papers describe the results of long-term efforts by two different groups to sequence the genome of DLBCL tumors.
A Groundbreaking Study
In a paper entitled “Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma” published in the journal Nature, Gascoyne, Marra and colleagues describe the results of a groundbreaking study. The researchers sequenced the entire DNA code from lymphoma tumors and compared the results to normal DNA obtained from the same patients. They were able to identify several genes that were mutated in the tumors but not in the normal DNA. Using these data, they were able to identify 109 genes with a potential role in lymphoma. Read the rest of this entry »
Cancer Care will present a Connect Education Workshop titled, “Update on Diffuse Large B-cell Lymphoma” via telephone on Wednesday, October 5, 2011 from 1:30 to 2:30 pm, Eastern Time. Weill Cornell’s Dr. John Leonard will be on the panel of experts.
The workshop is free of charge; no phone charges apply. However, pre-registration is required to secure a place on the call. Click here for more information and to register for the workshop.
Ari Melnick, MD, director of the Melnick Lab at Weill Cornell Medical College, was interviewed by the Lymphoma Research Foundation about his breakthrough research on a BCL6 inhibitor. Dr. Melnick discusses why this study is important for patients and what it could mean for the future of lymphoma research.
Click on the image below to read the Q&A.
Weill Cornell Research: Epigenetic Priming to Improve Chemotherapy Response Can Be Safely Administered in AML PatientsPosted: June 15, 2011
Researchers at Weill Cornell Medical Center have demonstrated that epigenetic priming of standard induction chemotherapy can be safely administered in an attempt to improve the response rate of patients with acute myeloid leukemia (AML).
Epigenetics refers to reversible alterations to DNA or DNA-associated proteins which affect gene expression, and epigenetic processes have been shown by researchers at WCMC and others to be disrupted in many types of cancer. Drugs currently available and approved by the FDA can target these abnormal epigenetic changes, and pretreatment with these drugs (epigenetic priming) might make cancer cells more vulnerable to chemotherapy.
In the research study recently published in Blood, the Journal of the of the American Society of Hematology, patients were treated with the drug decitabine prior to a standard induction of chemotherapy. The toxicity, or side effects, of chemotherapy plus decitabine was similar to that of chemotherapy alone. Although the primary purpose of the study was to evaluate the safety of adding decitabine, the epigenetic primer, to standard chemotherapy, the overall complete response rate was 83%, suggesting that decitabine-primed induction should be explored as a complementary approach to standard chemotherapy. Click here to read the published research paper.
There is the possibility that the approach of epigenetic priming could translate into therapeutic advantages in other forms of cancers. Many types of cancers have been shown to develop with abnormal epigenetic changes, including lymphoma. The lymphoma research group at Weill Cornell Medical Center is also exploring the strategy of epigenetic priming in patients with newly diagnosed aggressive B cell non-Hodgkin’s lymphoma, in hopes of improving on results of standard chemotherapy. Click here to read more about this study. Click here to read the clinical and research profile of Rebecca Elstrom, MD, the physician leading the lymphoma trial.
Several studies have demonstrated that rituximab (R) added to CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) can improve the outcomes of patients with diffuse large B-cell lymphoma (DLBLC). Nonetheless, there remains room for improvement.
A German study from the pre-rituximab era demonstrated that giving CHOP chemotherapy every two weeks (i.e., CHOP-14) was better than given CHOP every three weeks (i.e., CHOP-21) in patients older than 60 years of age. This type of therapy is also referred to as “dose-dense” therapy, and it is attractive because it theoretically allows less time for cancer cells to grow between chemotherapy cycles. The question of whether CHOP-14 would remain superior to CHOP-21 even after the addition of rituximab is the subject of two ongoing phase 3 clinical trials, one in France and one in the United Kingdom (UK). Dr. David Cunningham presented the results of the latter trial at the recent meeting of the American Society of Clinical Oncology (ASCO) in Chicago. After a median follow-up of about three years, there was no difference in survival between patients treated with R-CHOP-14 or R-CHOP-21. Click here to see the study abstract. These results are consistent with preliminary results from the French study presented in 2010 and confirm that R-CHOP 21 should remain the standard of care for most patients with DLBCL.
At Weill Cornell Medical Center, we believe that improvements in patient outcomes are likely to come from the addition of newer, targeted drugs to R-CHOP (click here to learn about our trial with azacitidine plus R-CHOP) rather than increasing the dose or density of older chemotherapy regimens.