By Jim Omel
Grand Island, NE
Excitement of support group leaders (SGLs) at the 56th American Society of Hematology (ASH) Annual Meeting and tremendous progress against myeloma come together in oral presentations, posters, and abstracts in which minimal residual disease (MRD) is discussed. IMF Chairman Dr. Brian Durie mentioned in a recent blog that there are 9 abstracts dealing with MRD assessment at ASH. Perhaps the most helpful is Abstract #3390. A strong consensus is building among experts that flow cytometry is the most cost-effective and practical laboratory method to measure MRD. This abstract explains the use of sensitive 8-color multidimensional flow cytometry to monitor MRD among elderly MM patients. It does this at amazing sensitivity… finding one cancerous myeloma cell among 1 million normal cells! A cutoff number is required for definition and the Spanish doctors chose a value to define MRD-negative as <20 clonal PCs among >2,000,000 white blood cells. This is obviously well within the sensitivity limits of MRD flow cytometry. The study represented by this abstract demonstrated MRD’s significant predictability by accurately estimating which treatment arm (sequential vs. alternating schema) would have a significantly longer TTP (time until disease progression). During the prestigious Ham-Wasserman lecture on Saturday, Prof. Jesus San-Miguel of the University of Navarra, Pamplona, Spain, explained the importance of 8-color flow as we evaluate MRD.
MRD is also the subject of intense evaluation by the NCI Myeloma Steering Committee (MySC). We are working to add this significant measure to clinical trials as a formal trial endpoint. A sub-committee of the MySC has met by telephone 6 times to consider how to formalize this. We also had a face-to-face meeting at ASH during which MRD was a significant topic of discussion. There is a strong sense of optimism that a reliably defined MRD test will soon be available in USA. Just as in lymphoma where data reported in Clinical Cancer Research (online October 14, 2014) show that MRD detection is a powerful independent predictor of PFS in patients with follicular lymphoma receiving conventional chemo-immunotherapy, MRD is also highly predictive of better outcomes in myeloma.
MRD evaluation was part of an Australian study (Abstract #2103). Abstract #2105 compares the detection of MRD by both MFC (flow) and NGS (next generation sequencing). Both methods have utility and both confirm the value of achieving MRD for myeloma patients. Abstract #2127 reports that achieving MRD-negative status in newly diagnosed MM patients treated with Kyprolis (carfilzomib), Revlimid (lenalidomide) and dexamethasone resulted in prolonged PFS (progression free survival). For those of us with this devastating cancer it is truly exciting to think how we have come from CR to sCR to now commonly talking about MRD negative. As IMF President Susie Novis said at the IMF’s Grant Awards Reception on Saturday night, we are so… so… so close to a cure!