Cancers are a huge focus for research. Millions of dollars every year are funneled into funding research that could improve treatment methods or find cures for cancer, including blood cancers. Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin’s lymphoma (NHL) accounting for about 30 percent of the NHL diagnoses in the United States. It is a very aggressive form of the cancer and thus is the focus of many research initiatives looking at treatments.
Current treatment for DLBCL is also aggressive since this form of cancer requires immediate action, but patient responses can vary immensely making the treatment process extra challenging for patients and providers. Typically, a combination of chemotherapy combined with the monoclonal antibody rituximab is the starting point. Sometimes this is combined with radiation therapy and can lead to remission for people with this type of lymphoma. For people who have relapsing DLBCL and do not enter remission after the initial treatment, there are many new medications currently in clinical trials. Due to the rapidly progressive nature of this type of lymphoma, it is necessary that there be a way to identify early on what treatment methods will be the most effective. Recently the Duke Cancer Institute identified genes that can help providers identify which treatments will be the most effective.
About the study
The researchers looked at tumor samples from 1,001 patients who had DLBCL. They extracted the DNA from the samples and then sequenced it to look at 150 genes that could help healthcare professionals identify whether or not chemotherapy will be an effective treatment for patients. Knowing if chemotherapy will be effective and if it is worth trying, can save time and money. More importantly, by not wasting time, it can increase the chances of remission. In addition, chemotherapy has severe side effects that are sometimes worse than the symptoms a patient has from the cancer itself. Avoiding these side effects can make the cancer battle a bit less traumatic for patients and their families.
The lead author of the study and professor of medicine Sandeep Davé said that, “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.” These advancements are essential since there is no method for early detection of lymphoma. Usually, by the time that lymphoma tumors are detected, the cancer has metastasized, and chemotherapy is required. The genes that were identified in the Duke study will help providers identify whether or not the patient will be responsive to chemotherapy, or if another treatment method should be used first. Davé explained that, “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.”
One of the benefits of this study is the size. With a sample size of 1,001 subjects, the results are more likely to accurately represent the DLBCL population as a whole. Additionally, Davé said that due to the size of the study mapping out how different mutations respond to chemotherapy will be easier. He said that differences in the genes of the tumors that people usually develop in only 5 to 10 percent, making analysis of responses to treatment difficult.
After the study was completed, researchers uploaded their results into a database so that other individuals can look at mutations and learn how effective chemotherapy may be as a treatment. Davé continued to say, “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.” Having this database available for providers and researchers to access will allow them to better provide individualized care to their patients.
Hopefully this research will empower providers and researchers to provide more effective care to their DLBCL patients in the initial phases of diagnosis. Having the ability to individualize treatment based on the specific characteristics of a patient’s cancer can lessen unnecessary adverse effects of chemotherapy and hopefully improve the quality of life for patients. This can also provide a measure of hope for patients who will know that they are starting a treatment method that has the potential to be effective.
This research indicates that similar studies could be done for other types of cancer. While mutations in lymphoma genes, and their responses to treatment methods may not be able to be directly applied to other types of cancer, this study could be motivation for researchers to repeat similar ones with other cancer types. Davé hopes that moving forward they will look at the genetics of all blood cancers and analyze the similarities and differences. Doing this will help shed some light on the more rare forms of leukemias and lymphomas that will unfortunately never be eligible for clinical trials due to the low number of people diagnosed.
Other genetic advances
Genetic advancements in the area of cancer research is not new, but is still very much a hot topic. Gene analysis has enabled medical professionals to identify who is at risk for what types of cancers and what treatments may or may not be effective. Advancements in molecular biology has led to the development of treatments that target cancer on the genetic level.
In October 2017 the FDA approved the second gene therapy for cancer, and the first for NHL. This new therapy is intended for people who try other treatment methods without success. “Yescarta” as it is called, is specifically modified for each patient. Each dose is made by taking a type of the patient’s white blood cells and modifying the genetic components of the medication to target and destroy the cancer cells. This is a whole new level of individualized care and rightfully so, people are excited about it. In clinical trials about 51 percent of people experienced complete remission after using the therapy. While this is a promising advancement in NHL treatment, no drug comes without side effects, and Yescarta’s can be severe.
The Yescarta side effects can include some dangerous neurological issues including headache, limb numbness, loss of vision and memory, and more. Therefore, while the drug is FDA approved, it comes with a Risk Evaluation and Mitigation Strategy (REMS) that requires professionals and organizations dispensing the therapy to be specially certified. The manufacturing company is also required to continue monitoring patients being treated with Yescarta.
Despite the side effects, this is still promising news, and hopefully moving forward more effective gene therapies with better side effect profiles will be developed.