Reprogramming Lymphoma Cells to Respond to Therapy

In a phase I clinical trial, researchers say they were able to reprogram treatment-resistant diffuse large B-cell lymphoma (DLBCL) so that it would respond to therapy.

High-grade lymphomas like DLBCL are generally treated with front-line chemotherapy and sometimes a stem cell transplant, but treatment is not always successful, and in fact many patients experience several treatment failures before succumbing to the disease, usually within two years of diagnosis.

About the study

According to a study published in the journal Cancer Discovery, researchers used the drug azacitidine. Leandro Cerchietti, M.D., and assistant professor at the Hematology and Oncology Division of Weill Cornell Medical College in New York said:

When lymphomas are formed, they shut down the cellular programs that sense that something is wrong in the cells. Once these fail-safe mechanisms that trigger cell death are shut down, it becomes difficult to kill the tumor with chemotherapy. Our study showed that using low concentrations of the DNA methyltransferase inhibitors decitabine or azacitidine, these fail-safe mechanisms can slowly be awakened to induce lymphoma cell death when chemotherapy is administered.

Phase I

Cerchietti and colleagues carried out a small phase I trial in patients with newly diagnosed DLBCL, enrolling 12 patients in all with nearly all considered high risk because of their age. The patients were treated with azacitidine in escalating doses for eight days before beginning six cycles of chemotherapy.

Of the 12 patients, 11 had a complete response (CR). Ten patients remained in remission for as long as 28 months.

Added Cerchietti:

We showed that aggressive lymphomas can be reprogrammed to a more benign disease. We think this work has the potential to change the standard of care for patients with aggressive lymphomas.

Source: Science Codex