Lymphoma patients who don’t respond to chemotherapy may be able to seek alternative treatment more quickly, thanks to new research from Duke.

Duke Cancer Institute researchers analyzed tumor samples from 1,001 patients with diffuse large B cell lymphoma, the most common form of the disease. After sequencing the tumors, the researchers identified 150 genes that could indicate ahead of time whether chemotherapy would be effective in fighting a patient's lymphoma. The scientists say knowing that chemotherapy will not be effective can help doctors devise different treatments sooner. 

“The goal was to really generate as comprehensive a road map as possible for understanding the role of different genes and responses to therapy, and to provide a prioritized list of targets so that we can prioritize new drug development and new clinical trials for these patients,” said Sandeep Davé, professor of medicine and the lead author of the study.

Although lymphoma is the most common blood cancer, patient response to therapies can vary widely, Davé explained. And unlike lung cancer or breast cancer, where early detection is key, there is no method for early identification of lymphoma tumors. By the time lymphoma is diagnosed, the tumors have spread and all patients need chemotherapy. 

However, Davé said chemotherapy is usually effective for just about half of all lymphoma patients. When patients do not respond to the therapy, doctors then try other treatments. But the genes pinpointed in the Duke study will help streamline the process because they can tell doctors about a patient's responsiveness to chemotherapy before they have even started the treatment. 

“So with our study, it’s possible to identify some of these patients who are unlikely to respond to up-front chemotherapy, and at least start thinking early about what we’re going to do next and possibly enroll them in clinical trials early rather than late,” he said.

Davé noted that this study was one of the largest genetic studies of any disease. He said that differences in the genes of tumors develop infrequently in patients, with most mutations occurring at a frequency of about just five to 10 percent. With a large sample size—more than 1,000 patients—it is easier to map out different mutations respond to chemotherapy.  

Researchers uploaded the genetic information, which they collected onto an interactive online database. Davé explained that the database allows individuals to select different mutations and learn more about the chemotherapy outcomes for certain mutations. 

“So these are questions that are not directly answered in the paper, but thanks to the [database] and its interactive nature, people can access these data in creative and new ways that allow them to specifically hone in on characteristics of their patients and how they might resemble our cohort of 1,000,” Davé said.

Although the information identifies the full spectrum of mutations in the specified lymphoma genes, Davé noted that it’s hard to say whether the gene mutations apply to other cancers.

Davé said that the next step is to look at all blood cancers and comprehensively analyze their similarities and differences.

“Some of these cancers are quite rare,” Davé said. “And so there will never be a clinical trial for specific leukemias and lymphomas, but if you can draw lines between different leukemias and lymphomas…then you can apply therapies that are already developed in another type of cancer in these patients.”