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.
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.
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.
Update: this study is closed to enrollment.
Bruton tyrosine kinase (Btk) is an enzyme that plays a crucial role in the development of the normal immune system. Recent studies indicate that Btk may also play a role in many B-cell lymphomas.
PCI-32765 is an investigational drug that irreversibly inhibits Btk. A phase 1 trials performed at several sites, including Weill Cornell Medical Center, demonstrated that PCI-32765 was well tolerated with minimal side effects.
In this phase 2 study, we are evaluating the efficacy of PCI-32765 (four pills take once daily) in patients with previously treated mantle cell lymphoma. We hope to learn how well PCI-32765 works and more about its side-effect profile.
To learn more about this study, please contact June Greenberg, RN at (212) 746-2651 or email June at firstname.lastname@example.org.
Click here to view the clinical and research profile of Peter Martin, MD, the physician leading the study at Weill Cornell Medical Center.