Therapy Improves Survival for Younger People With Cancer

New evidence suggests that adding the targeted therapy ibrutinib (Imbruvica) to a standard chemotherapy regimen can improve how long some younger people with a specific form of diffuse large B-cell lymphoma (DLBCL) live. The findings, published in Cancer Cell, come from a new analysis by NCI researchers of a previously conducted phase 3 clinical trial.

Initial results from that study, known as the PHOENIX trial, showed that combining ibrutinib with the standard chemotherapy regimen did not help patients with a form of DLBCL called non-GCB DLBCL to live longer overall. However, by analyzing tumor biopsy samples from patients in the trial, NCI researchers have now shown that younger patients with specific genetic subtypes of non-GCB DLBCL, called MCD and N1, had an exceptional response to the treatment combination, with all such patients alive without disease 3 years after diagnosis.

“People thought the trial didn’t work,” said Dr. Louis Staudt of NCI. “But there was something interesting going on. If you just considered younger patients under the age of 60, they had a real benefit from ibrutinib, and we now understand why.”

DLBCL is the most common type of lymphoma, accounting for 40 percent of lymphoma cases worldwide. This fast-growing cancer affects B cells, a type of white blood cell, and usually starts in the lymph nodes. People with DLBCL are typically treated with a chemotherapy regimen known as R-CHOP, but it’s not effective for all people with DLBCL.

In the 2000s, to better understand individual variation in treatment response, researchers analyzed the patterns of gene activity in DLBCL tumors. They discovered three molecular subgroups of DLBCL that each respond differently to chemotherapy. 

In a previous phase 2 clinical trial involving patients with relapsed DLBCL, researchers found that treatment with ibrutinib alone resulted in tumor shrinkage in 37 percent of patients with the ABC subtype but only 5 percent of those with the GCB type. Subsequently, researchers launched the PHOENIX trial to evaluate the impact of adding ibrutinib to R-CHOP in patients with newly diagnosed non-GCB DLBCL. 

“For years we have only had chemotherapy and rituximab to offer these patients,” Staudt said. “Now, we hope that adding ibrutinib to current therapy may give younger patients a better chance of surviving this aggressive cancer.”