Project Term
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Project Summary
Improving survival for patients with diffuse large B-cell lymphoma requires tailoring treatment to lymphoma genetic heterogeneity, addressing minimal residual disease (MRD), and bringing safer, effective therapies for frail patients who cannot tolerate aggressive regimens. I address these challenges with genomic subtype targeted treatment, bispecific antibody to eliminate MRD, and novel treatment for frail patients. My goal is to improve outcomes by bringing biomarkers to standard of care.
Lay Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma with annual estimated new cases of approximately 25,000. Current standard fist line treatment of DLBCL is chemoimmunotherapy such as R-CHOP, EPOCH-R or polatuzumab-R-CHP. However, approximately 30-40% of patients will experience relapse, some even after achieving complete response, and those who have relapsed disease have poor outcomes. Studies have found that DLBCL is a very heterogeneous disease and that DLBCL subtypes have different response and risk of relapse by subtype and treatment. However, we haven’t been able to test for these subtypes fast enough to pick the right treatment for each patient. Therefore, there is an unmet need to develop and streamline faster and more reliable biomarker testing in DLBCL, pre-treatment to select treatment wisely based on subtype and post-treatment to make action for patients with high risk of relapse.
To help solve this problem, we completed a project called "Test-the-Test" and showed that we could get results from genetic testing quickly enough to make a difference in treatment decisions. After treatment, it’s also important to know if any lymphoma cells are still present, even if they cannot be seen by imaging study such as PET scan. This is called minimal residual disease (MRD), and if left untreated, it can lead to relapse. To detect MRD, we are using a highly sensitive blood test called PhasED-seq, which has been accurate in predicting who are at risk of lymphoma relapse.
To improve outcomes for DLBCL patients, we are running three clinical trials. The first trial aims to select best standard first line treatment based on their genetic testing results. The second trial focuses on patients at high risk of relapse, identified by the presence of MRD in blood after treatment, and treat with bispecific antibody called glofitamab. The third trial is using bispecific antibody called epcoritamab with less intensive chemotherapy for frail patients predicted to not tolerate standard chemotherapy, to see if it can provide effective treatment with fewer side effects. This research program can change the way we treat DLBCL by allowing doctors to make decisions based on specific biomarkers and patient characteristics - paving the way for precision medicine, where treatment is tailored to each individual’s unique lymphoma. Our ultimate goal is to give patients the best possible chance of long-term survival with the least amount of side effects.
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