As treatments lead to deeper and more sustained responses, new markers for measuring and predicting treatment response that are more sensitive than current endpoints are required.[1]
This page will explore response measurement criteria for Multiple Myeloma (MM). In addition, it will cover minimal residual disease (MRD), which is currently being investigated as a potential surrogate endpoint for survival outcomes in clinical studies.[2]
The International Myeloma Working Group (IMWG) response criteria were introduced to help standardise assessment of response in MM and have since been universally adopted in myeloma clinical trials.[3][4][5]
Over time a number of important changes have been made to the IMWG uniform response criteria, including: a more stringent definition of complete response (CR) to treatment based on the availability of more sensitive analytical techniques; the introduction of a very good partial response (VGPR) category, to help distinguish patients who have had near disappearance in their monoclonal (M)-spike but are still immunofixation-positive from those who have merely had a 50% reduction in their serum M-spike; and, in 2016, the incorporation of MRD assessment.[3][4][5]
A complete response defined as the negative immunofixation on the serum and urine, disappearance of any soft-tissue plasmacytomas and <5% plasma cells in the bone marrow[4]
The current IMWG uniform response criteria also include the following categories for deeper responses than CR:[3][4]
VGPR is defined as serum and urine M-component detectable by immunofixation but not on electrophoresis, or ≥90% reduction in serum M-component plus urine M-component <100 mg/24 hour.[4]
PR is normally defined as ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours. If the serum and urine M-protein are unmeasurable, a ≥50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. If serum and urine M-protein are unmeasurable, and the serum FLC assay is also unmeasurable, ≥50% reduction in bone marrow plasma cells is required in place of M-protein, provided baseline percentage was ≥30%.
In addition to the above criteria, if present at baseline, a ≥50% reduction in the size of soft-tissue plasmacytomas is also required.[4]
SD is defined as any state that does not meet the criteria for CR, VGPR, PR or progressive disease (PD).[3]
PD is defined as an increase of >25% from lowest response value in any one or more of the following:[3]