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.
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.
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
The current IMWG uniform response criteria also include the following categories for deeper responses than CR:
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.
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.
SD is defined as any state that does not meet the criteria for CR, VGPR, PR or progressive disease (PD).
PD is defined as an increase of >25% from lowest response value in any one or more of the following:
An increasing number of clinical trials are using MRD-negativity assessment as a primary or secondary endpoint.
Further clinical trials are being conducted to understand whether MRD-negative status can be used to assess treatment response and to guide treatment decisions in clinical practice.
Currently, an MRD consortium, the International Independent Team for Endpoint Approval of Myeloma MRD (i2 TEAMM), is developing a meta-analysis based on primary source data to be provided by investigators examining MRD in randomised Phase III trials. This meta-analysis will be submitted to the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the designation of MRD as a surrogate endpoint for PFS and OS.
Early diagnosis is critical in MM. An array of diagnostic methods can be used to characterise a patient’s MM, allowing for individualised treatment and management.
Treatment aims to extend survival by stopping or slowing growth and spread of myeloma cells. In addition, therapy can alleviate patients’ symptoms and complications, and improve quality of life.