Stratified treatment of newly diagnosed MCL based on the presence or absence of high risk features utilizing non-cytotoxic agents.
Tycel Phillips
MDBeckman Research Institute of the City of Hope
Project Term: July 1, 2022 - September 30, 2027
We believe that regimens without chemotherapy can induce significant and durable remissions in patients with Mantle cell lymphoma (MCL). We will confirm this hypothesis by conducting two clinical trials stratified by the presence or absence of high risk features. We will utilize BH3 profiling and MRD testing to assist with predicting treatment response and remission. Our goal is to verify the efficacy of our regimen and prove the utility of BH3 profiling and MRD testing in outcome prediction.
Mantle Cell lymphoma (MCL) is a rare form of non-Hodgkin Lymphoma that unfortunately is incurable with the treatments that are used to treat patients today. Treatment for this cancer almost exclusively involves drugs (chemotherapy) that damage all fast growing cells whether cancerous or not. This can lead to unwanted side effects that limit this type treatment to a select group of patients. Also we we know there is a group of patients whom we deem to be "high risk" that will have a very limited response to this form of treatment. In a previous study we evaluated a regimen using a limited course of oral medications to treat previously untreated patients with MCL. The results of this study are promising and appear durable. Given this we plan to expand our original study to further explore the effectiveness of these drugs in a larger pool of patients to better compare our outcomes to what has been previously reported with treatments that utilize chemotherapy. In a second study we have designed a treatment for the population of patients mentioned previously that is known to have poor outcomes when treated with chemotherapy. Recent data demonstrates that treatments which utilize our immune system appear effective in "high risk" patients. We will utilize an antibody that functions to target the immune system against MCL together with our oral medication regimen in a second study we have designed specifically for "high risk" patients that we know have poor outcomes when treated with chemotherapy.. Importantly for both studies will evaluate for clearance of the cancer using a special test that will identify tiny remnants of the cancer in blood and will attempt to identify patients who might not respond to the proposed treatment. We believe that we will achieve three major goals. 1. We will demonstrate that we can obtain comparable or better results without exposing patients to chemotherapy and its associated side effects. With this we would aim to treat MCL while providing an opportunity not negatively impact the patients quality of life. 2. We feel that for high risk patients we will be able to establish a treatment regimen with superior and more durable responses to what has been demonstrated thus far with chemotherapy. 3. We believe that our secondary tests will allow for better identification of appropriate patients for this type of treatment and allow for improvement in our ability to predict long term response as compared to what is our current standard.