“No research is ever quite complete. It is the glory of a good bit of work that it opens the way for something still better, and this repeatedly leads to its own eclipse.” — M. Gordon
As new drugs and therapies have become available in the last ten years for the treatment of multiple myeloma, a test for evaluating the efficacy of these therapies is important. Currently, we get tested periodically for proteins by immunofixation electrophoresis to determine the status of our M protein. MRD is intended to ascertain deep responses to combination therapies by counting the myeloma cells present in the bone marrow after a clinical response has been achieved. This method can determine the myeloma cells that are beyond detection by usual blood tests currently used.
Two methods of establishing MRD are described. Flow cytometry which is more readily available and is less sensitive can identify one myeloma cell per one hundred thousand cells in the bone marrow sample. Sequencing which is more sensitive and is a better technology can identify one myeloma cell per one million cells in the bone marrow sampled. A negative sequencing result is consistent with a deep response and consistent with a longer overall survival. MRD testing outside of clinical trials is not recommended at this time. MRD negativity does not suggest a cure nor does MRD positivity suggest fatal disease. Currently MRD results are not used to manage therapy, that is, if negative, does treatment stop or if positive, does treatment intensify? More research is needed to understand how to use this test in clinical practice. MRD has been proposed as an end point for drug approval for treating multiple myeloma. Proteomic studies are being evaluated that could be done on blood or urine samples rather than a dreaded bone marrow biopsy.
The annual meeting of The American Society of Hematology (ASH) will be held in Orlando, Florida this year in early December. Again, there will be hundreds of abstracts on the new protocols for induction therapy, maintenance therapy and treating relapsed myeloma. These will include chemotherapy, corticosteroids, immunomodulatory agents, proteasome inhibitors, nuclear export inhibitors, histone deacetylase inhibitors, monoclonal antibodies, as well as CAR T-cells therapies, Bi-specific T-cell engagers (BiTEs) and CRISPR/Cas 9 edited T cells. We will be looking for deep responses (remission) and MRD negative results in these investigative studies.
We are hoping that a “good bit of work opens the way for still something better” in improving the understanding and managing multiple myeloma in the newly diagnosed and relapsed patients.