Tag: Weill Cornell

Lymphoma in the News: R-CHOP 21 Remains Standard of Care for Diffuse Large B-Cell Lymphoma

By Peter Martin, MD

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 rather than increasing the dose or density of  older chemotherapy regimens.

Weill Cornell Research: ALK Inhibitors Completely Eradicate DLBCL with ALK Translocation in Laboratory Animals

In a significant finding recently published in PLoS One, researchers at Weill Cornell Medical Center showed that ALK inhibitors (drugs that act on tumors with the protein ALK) could completely eradicate Diffuse Large B-Cell Lymphoma (DLBCL) with ALK mutation in laboratory animals. This is an important finding considering that patients with DLBCL with ALK mutations are resistant to common chemotherapy treatments.

Patients diagnosed with ALK positive DLBCL may, therefore, be candidates for therapeutic trials of ALK inhibitors. The incorporation of ALK status determination into the diagnosis of DLBCL could help identify these patients more readily. There are several ALK inhibitors under clinical testing for ALK positive tumors.

Background

BCL6 is the most frequent oncogene (a gene that has the ability to cause cancer) in Diffuse Large B-Cell Lymphoma (DLBCL). However in a proportion of DLBCL other genes play a leading role in the oncogenic process. In an effort to personalize the treatment for patients with DLBCL, we found that a protein called ALK plays an oncogenic role in a subset of DLBCL.

We established and characterized the first ALK positive DLBCL line with a mutation that causes ALK to be expressed and active at very high levels, causing tumor cells to proliferate (reproduce rapidly). This cell line was obtained from the bone marrow tissue of a patient diagnosed with DLBCL. We developed pre-clinical animal models of DLBCL with ALK mutation, and we treated them with specific ALK inhibitors. As described above, the research showed that ALK inhibitors could completely eradicate DLBCL with ALK mutation in animals.

Click here to read the published research paper.

Weill Cornell Investigational Drug Shuts Down Aggressive Form Of Leukemia That Affects Children

In a significant breakthrough published recently in Nature, researchers at Weill Cornell Medical College and the University of California, San Francisco, have been able to overcome resistance of a form of leukemia to targeted therapy, demonstrating complete eradication of the cancer in cell and animal studies.

The study shows that an investigational drug, RI-BPI, developed at Weill Cornell, in combination with the drug Gleevec shut down stem cells responsi ble for about one-third of acute lymphoblastic leukemia (ALL), a cancer of white blood cells that affects young children as well as older adults. This form of ALL has the so-called Philadelphia chromosome, which is also found in chronic myelogenous leukemia (CML). But while Gleevec has greatly improved survival in CML, it has had a less dramatic effect in ALL, and most patients still die within a relatively short time frame.

That prognosis may change given these results, says co-senior investigator Dr. Ari Melnick, associate professor of medicine and director of the Raymond and Beverly Sackler Center for Biomedical and Physical Sciences at Weill Cornell Medical College, and a hematologist-oncologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. Dr. Melnick and his colleagues developed RI-BPI, and they have shown its potent effects in non-Hodgkin’s lymphoma (NHL) with no toxicity to normal cells. The drug targets the transcription factor BCL6, a master regulator of hundreds of genes that provides strong growth signals to NHL cells.

“I am surprised, and extremely glad, to see that RI-BPI has such strong activity in a leukemia. This opens up the possibility that the agent will have similar beneficial effects in other tumor types,” says Dr. Melnick.

Click here to read the press article describing the study results. Click here to read the published research paper.

Background on the development of RI-BPI at Weill Cornell Medical Center: Diffuse Large B ell lymphoma (DLBCL) is a common and aggressive subtype of lymphoma that is frequently associated with deregulation of the oncogene BCL6 (oncogene is a genetic material that carries the ability to induce cancer). Deregulated BCL6 activity keeps B cells in a rapidly proliferating (reproducing) state. The high levels of BCL6 expression in DLBCL coupled with the low or nil expression of BCL6 in normal cells have made BCL6 an attractive candidate for anti-cancer drug development.

Personalized lymphoma medicine offers the hope that by identifying lymphoma-causing mutations in critical regulatory genes, we can target these mutant proteins to cure lymphoma while limiting the side effects. Continue reading “Weill Cornell Investigational Drug Shuts Down Aggressive Form Of Leukemia That Affects Children”