Researchers from Weill Cornell Medical College and New York–Presbyterian Hospital in New York City have found a targeted therapy that makes chemotherapy more effective against an aggressive lymphoma that often relapses and kills patients within 2 years.
In their study, published in Cancer Discovery, patients experienced a remission and stayed disease-free as long as 28 months after taking azacitidine, a commercially available drug designed to reawaken molecular mechanisms that trigger cell death but that are switched off as cancer progresses. Investigators determined that pretreating patients' aggressive lymphoma with the drug enables the death signal to turn back on when it is triggered by chemotherapy.
The proof-of-concept study of 12 high-risk patients with diffuse large B-cell lymphoma (DLBCL) was led by Peter Martin, MD, assistant professor of medicine and a hematologist/oncologist at New York–Presbyterian Hospital. All patients were given low doses of azacitidine for 5 days before receiving standard chemotherapy. Eleven of the patients achieved a complete remission of their cancer, while 10 remained cancerfree for up to 28 months.
Approximately one-third of patients with DLBCL do not respond to initial chemotherapy or relapse, and because the majority will die within 2 years of diagnosis, new treatments are urgently needed, the research team says. They add that this new approach could potentially be applied to other tumor types.
The team studied azacitidine due to increasing evidence that most of these cancers eventually become resistant to chemotherapy. This genetic resistance is caused in part by the addition of silencing chemicals called methyl groups, which prevent chemotherapy from activating death-inducing genes. Azacitidine removes the methyl groups, allowing chemotherapy to do its job by activating these death genes.
Researchers say they are in the process of further personalizing the treatments and are planning to expand the study to additional DLBCL patients in a multicenter clinical trial. They also plan to study their pretreatment strategy in other tumors, including other lymphomas.