Last Friday, the MMRF and Memorial Sloan Kettering Cancer Center (MSKCC) co-hosted the Advances in Minimal Residual Disease (MRD) Testing in Multiple Myeloma meeting. This meeting, the fourth in the series, brought together 70 representatives from the MMRF, academia, the pharmaceutical industry, and government agencies to discuss progress in the last year toward standardization and validation of different methods of MRD testing, and approval of MRD testing by the US FDA as an approved measurement and endpoint in clinical trials. Find out more about MRD testing and how MMRF is helping win approval for this test here.
Since the group convened a year ago, participants published a white paper in the scientific journal Cancer Research, summarizing the state of the science in MRD and critical future directions, both toward validating MRD as a clinical endpoint, and with the goal of eventually incorporating the measurement of MRD into standard practice in the treatment of MM.
This meeting focused on the following key areas:
- – In several large ongoing clinical trials either in the smoldering, newly diagnosed (DFCI IFM) or relapse setting (CASTOR, POLLUX), results showed that achieving MRD negativity (fewer than 1 multiple myeloma cell found in 1 million bone marrow cells) was correlated with a longer period of disease remission before relapse occurs, , regardless of what drug combination the patients received. These studies are showing that depth of response is most critical, rather than how one gets to those MRD negative deeper responses.
- – The experience of clinicians using MRD testing for their patients differed. Some doctors measured MRD in every patient, and it was covered by insurance. Others used MRD measurement rarely, and the test was not always covered by insurance. The panel concluded that MRD is not used frequently in clinical practice despite its prognostic value, pointing to the need to increase efforts to gain approval for this important test to improve outcomes for MM patients. There was also significant discussion on the need for data to guide what clinicians should do if a patient suddenly changes from MRD negative to MRD positive. Does that alone indicate treatment should be changed? What about if a patient is on a clinical trial? Discussion around these points underscored the need for generating additional data to resolve these issues.
- – While the standard approaches for MRD testing involve analyzing bone marrow aspirates from patients, data presented on a number of MRD imaging approaches as well as on blood-based biopsies (where patients’ blood is used to test for MRD measurement as opposed to their bone marrow) showed that new options may soon be available to augment or someday replace the bone marrow aspirate.
- – The FDA continues to express eagerness to work with the MMRF and the MM community on making MRD a clinical trial endpoint. In order to do so, a collaborative effort with the Agency is needed, to evaluate data from ongoing trials to validate MRD in MM along the lines of what has been successfully achieved in breast cancer and in follicular lymphoma.
At the conclusion of the meeting, the group collectively decided that an effort to compile data from ongoing clinical trials which evaluated MRD should be immediately undertaken. This data will be provided to the FDA as soon as possible, with the goal to achieve approval for MRD testing as a new clinical trials endpoint within a year.