Combination Therapy Incorporating 3 New Agents Shows Promise As Treatment for Aggressive Lymphoma

BUFFALO, N.Y. — New research from Roswell Park Comprehensive Cancer Center shows that promising cancer drugs used in combination can have significant therapeutic impact on a particularly aggressive subtype of diffuse large B-cell lymphoma (DH-DLBCL) in preclinical studies. The researchers will present their findings at the American Association for Cancer Research (AACR) Annual Meeting 2016, to be held April 16-20 in New Orleans.

Priyank Patel, MD, a fellow in the Department of Medicine at Roswell Park, is the first author and Francisco Hernandez-Ilizaliturri, MD, Clinical Chief of the Institute’s Lymphoma/Myeloma Service, is the senior author of “Investigating novel targeted therapies for double hit diffuse large B-cell lymphoma (DH-DLBCL)” (abstract 3038), which will be presented on Tuesday, April 19, at 8 a.m. CDT.

Diffuse large B-cell lymphoma, the most common type of non-Hodgkin lymphoma, is an aggressive form of lymphoma. This research team reviewed a database of 650 patients with diffuse large B-cell lymphoma, identifying 36 patients whose tumors had two or more aberrant genes. Patients with mutations of the c-MYC, BCL2 and/or BCL6 genes — a subtype known as “double-hit lymphoma” — have especially have poor outcomes when treated with standard chemotherapy. The scientists evaluated the effectiveness of three novel anticancer drug candidates that targeted those proteins. In preclinical studies, the therapeutic agents ABT-199, JQ-1 and carfilzomib induced cell death in a dose- and time-dependent manner. Significant synergistic activity was observed when researchers combined ABT199 with carfilzomib and, to a lesser extent, with JQ1 in cancer cell lines.

“Increasing knowledge of genetics and molecular pathways has helped us identify a subgroup of patients who harbor aggressive aberrant gene mutations. Understanding the mechanisms of action and clarifying how these potential therapies work to inhibit cancer cell growth may result in improved outcomes for patients diagnosed with this aggressive type of lymphoma,” says Dr. Hernandez-Ilizaliturri.

“As we continue to gain more insight into the finer aspects of cancer biology by understanding the molecular pathways through which the cancer cells grow, we can identify strategies to effectively exploit the growth mechanism of these tumors and hopefully translate that knowledge into improved cure rates for our patients,” adds Dr. Patel.

The research was funded, in part, by a generous donation from Carl and Noreen Spezio.

###

The mission of Roswell Park Comprehensive Cancer Center is to understand, prevent and cure cancer. Founded in 1898, Roswell Park is one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit www.roswellpark.org, call 1-800-ROSWELL (1-800-767-9355) or email AskRoswell@Roswellpark.org. Follow Roswell Park on Facebook and Twitter.