Dr Cornell and his team found that the introduction of immunomodulatory agents such as thalidomide, lenalidomide, and pomalidomide as well as the proteasome inhibitors bortezomib and carfilzomib have helped contribute to a steady improvement in overall survival. The median survival is now estimated to be 62 months for those with stage 1 disease, 44 months for those with stage 2 disease, and 29 months for those with stage 3 disease as determined by the International Staging System.2

Medical Oncologist Ravi Vij, MD, professor of medicine, Division of Oncology, Section of Bone Marrow Transplantation at Washington University School of Medicine in St. Louis, MO, said MRD testing is only being performed at his institution in the context of clinical trials.


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He said trials have shown that patients who achieve MRD negativity post-transplant have better progression-free survival and overall survival. However, he said clinicians do not have enough information yet to know how to best test for MRD: multi-parameter flow cytometry vs NGS technologies.

A Call for Standardization

Leona Holmberg, MD, who is with the Fred Hutchinson Cancer Research Center, Clinical Research Division in Seattle, WA, said there are many weakness in all the methods of MRD testing.

“I don’t think it is ready for prime time and I don’t think it is appropriate for clinical decisions. I think we have to define MRD better,” Dr Holmberg told Cancer Therapy Advisor. “There are too many questions unanswered and we don’t have standardization from center to center and so I don’t think we can make decisions based on MRD testing.”

She said another problem can be with the sample area. It may that an area has been picked for MRD testing where there may or may not be disease. Dr Holmberg said that raises the question of whether there is a need to test multiple areas.

“NGS does have a potential to overcome the sampling problem, but it may be that there is a low concentration in the blood so that may be a challenge. You have to still figure out your optimal sample sites. Genetic instability is an issue because there is clonal diversity,” said Dr Holmberg.

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She noted the timing of when to use these tests is something that has to be examined She said with MM the question becomes whether the best time is 30 days post-transplant for MRD testing or is that too early and 80 to 100 days may be better.