Our latest quiz highlights the role of testing for minimal residual disease in the management of multiple myeloma.
B.Minimal residual disease
As noted by Ola Landgren, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York and others, in recent years the approval of several new, less-toxic agents for management of multiple myeloma has prompted the development of combination first-line treatment regimens and testing for minimal residual disease (MRD) has become key in clinical trial assessments of investigational therapies, particularly for younger and fit newly diagnosed patients.
D. Clinical trials
MRD testing is currently used as a treatment response–assessment tool for clinical research. MRD measurements are strongly associated with progression-free survival (PFS). In clinical trials, MRD negativity has been shown to predict PFS among newlydiagnosed older patients who are not candidates for transplantation; patients with relapsed and refractory disease; and younger, fit patients. Because of these findings, as well as the biological heterogeneity of multiple myeloma and the growing number of treatment options, experts anticipate that MRD assessments rather than predefined treatment sequences will guide disease management in the future. Methodological validation and standardization are needed, however, before MRD assessment can become a tool for routine clinical management of multiple myeloma.
D.All of the above
In addition to flow cytometry–based panels, more sensitive MRD assays based on bone marrow, circulating myeloma cells, and cancer DNA sequencing are under development-as are magnetic resonance imaging and functional (PET/CT) imaging techniques.
Some researchers advocate the adoption of MRD negativity as a surrogate endpoint for regulatory approval because of its strong association with PFS, and many expect the FDA to do so in the coming few years. The use of surrogate endpoints like PFS for regulatory drug approvals remains very controversial, however-partly because PFS itself does not always predict overall survival time.
Flow cytometry-based MRD can reach a detection sensitivity of 1 myeloma cell per 100,000 bone marrow cells, whereas DNA-based MRD assays current offer a sensitivity of 1 myeloma cell in 1,000,000 bone marrow cells. MRD assessed using more sensitive assays is more strongly associated with PFS.