The International Myeloma Working Group established the below criteria in order to:
- facilitate precise comparisons of efficacy between new treatment strategies in trials
- incorporate the serum free light chain (FLC) assay to include assessment of patients with oligo-secretory and non-secretory disease
- provide stricter definitions for CR (complete response)
- provide classifications that would improve detail and correct inconsistencies in prior response criteria.
The following criteria reconcile various previously used systems for assessing response and have been universally adopted.
|sCR||CR as defined below plus normal FLC ratio and absence of clonal cells in bone marrow3 by immunohistochemistry or immunofluorescence4|
|CR||Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow3|
|VGPR||Serum and urine M-protein detectable by immunofixation but not on electrophoresis or > 90% reduction in serum M-protein plus urine M-protein level < 100 mg/24 h|
|PR||> 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or to < 200 mg/24 h
If the serum and urine M-protein are unmeasurable,5 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 not measurable, and serum free light assay is also not measureable, > 50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was > 30%
In addition to the above listed criteria, if present at baseline, a > 50% reduction in the size of soft tissue plasmacytomas is also required
|No change/Stable disease||Not meeting criteria for CR, VGPR, PR, or progressive disease|
|Progressive disease5||Increase of > 25% from lowest response value in any one or more of the following:
|Relapse||Clinical relapse requires one or more of:
Direct indicators of increasing disease and/or end organ dysfunction (CRAB features).6 It is not used in calculation of time to progression or progression-free survival but is listed here as something that can be reported optionally or for use in clinical practice
|Relapse from CR5 (To be used only if the end point studied is DFS)8||Any one or more of the following:
1 BGM Durie et al. International uniform response criteria for multiple myeloma. Leukemia (2006) 1-7.
Adapted from Durie BGM, et al. Leukemia 2006; 20: 1467-1473; and Kyle RA, Rajkumar SV. Leukemia 2008;23:3-9.
Note: A clarification to IMWG criteria for coding CR and VGPR in patients in whom the only measurable disease is by serum FLC levels: CR in such patients is defined as a normal FLC ratio of 0.26–1.65 in addition to CR criteria listed above. VGPR in such patients is defined as a >90% decrease in the difference between involved and uninvolved free light chain (FLC) levels.
3 Confirmation with repeat bone marrow biopsy not needed.
4 Presence/absence of clonal cells is based upon the kappa/lambda ratio. An abnormal kappa/lambda ratio by immunohistochemistry and/or immunofluorescence requires a minimum of 100 plasma cells for analysis. An abnormal ratio reflecting presence of an abnormal clone is kappa/lambda of > 4:1 or < 1:2.
5 All relapse categories require two consecutive assessments made at anytime before classification as relapse or disease progression and/or the institution of any new therapy. In the IMWG criteria, CR patients must also meet the criteria for progressive disease shown here to be classified as progressive disease for the purposes of calculating time to progression and progression-free survival. The definitions of relapse, clinical relapse and relapse from CR are not to be used in calculation of time to progression or progression-free survival.
6 For progressive disease, serum M-component increases of >1 gm/dL are sufficient to define relapse if starting M-component is >5 g/dL.
7 Relapse from CR has the 5% cut-off versus 10% for other categories of relapse.
8 For purposes of calculating time to progression and progression-free survival, CR patients should also be evaluated using criteria listed above for progressive disease.