Weill Cornell’s Dr. Rebecca Elstrom is attending the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland and provides this update:
Researchers from MD Anderson Cancer Center reported results of a study of the combination of rituximab and lenalidomide in relapsed and refractory mantle cell lymphoma (MCL) at the 11th International Conference on Malignant Lymphoma on Thursday, June 16. The study included 52 patients treated on a combined phase 1/phase II study. The researchers found that more than half (57.8%) of patients responded to treatment, and most responses lasted for at least 18 months. The combination was very well tolerated, with few bothersome side effects. These results are striking for this group of patients, especially as many had not responded to previous therapy.
The combination of rituximab and lenalidomide is of interest because both drugs work, at least in part, by promoting the patient’s immune system to destroy lymphoma cells, and laboratory studies have suggested that each drug may make the other work better. In addition to mantle cell lymphoma, this combination is being investigated in other B-cell lymphoma subtypes.
Weill Cornell Medical Center is conducting a study of the combination of rituximab and lenalidomide in follicular lymphoma. The study is sponsored by The Cancer and Leukemia Group B (CALGB) and is being led at Weill Cornell by Dr. Elstrom. (Update: this study is closed to enrollment.)
By Rebecca Elstrom, MD
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.
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.