InternationalMyelomaWorkingGroup(IMWG)Uniform
ResponseCriteriaforMultipleMyeloma1
TheInternationalMyelomaWorkingGroupestablishedthebelowcriteriainorder
to:
facilitateprecisecomparisonsofefficacybetweennewtreatmentstrategies
intrials
incorporatetheserumfreelightchain(FLC)assaytoincludeassessmentof
patientswitholigosecretoryandnonsecretorydisease
providestricterdefinitionsforCR(completeresponse)
provideclassificationsthatwouldimprovedetailandcorrectinconsistencies
inpriorresponsecriteria.
Thefollowingcriteriareconcilevariouspreviouslyusedsystemsforassessing
responseandhavebeenuniversallyadopted.
Response
IMWG criteria
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
MR
NA
1BGMDurieetal.Internationaluniformresponsecriteriaformultiplemyeloma.Leukemia(2006)17.
No
Not meeting criteria for CR, VGPR, PR, or progressive disease
change/Stable
disease
Plateau
NA
Progressive
Increase of 25% from lowest response value in any one or more of the following:
disease5
Serum M-component and/or (the absolute increase must be 0.5 g/dL)6
Urine M-component and/or (the absolute increase must be 200 mg/24 h)
Only in patients without measurable serum and urine M-protein levels; the
difference between involved and uninvolved FLC levels. The absolute increase
must be > 10 mg/dL
Bone marrow plasma cell percentage; the absolute percentage must be 10%7
Definite development of new bone lesions or soft tissue plasmacytomas or
definite increase in the size of existing bone lesions or soft tissue
plasmacytomas
Development of hypercalcaemia (corrected serum calcium > 11.5 mg/dL or 2.65
mmol/L) that can be attributed solely to the plasma cell proliferative disorder
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
1. Development of new soft tissue plasmacytomas or bone lesions
2. Definite increase in the size of existing plasmacytomas or bone lesions. A definite
increase is defined as a 50% (and at least 1 cm) increase as measured serially by
the sum of the products of the cross-diameters of the measurable lesion
3. Hypercalcemia (> 11.5 mg/dL) [2.65 mmol/L]
4. Decrease in haemoglobin of 2 g/dL [1.25 mmol/L]
5. Rise in serum creatinine by 2 mg/dL or more [177 mol/L or more]
Relapse from
Any one or more of the following:
CR5 (To be used
only if the end
Reappearance of serum or urine M-protein by immunofixation or electrophoresis
point studied is
Development of 5% plasma cells in the bone marrow7
DFS)8
Appearance of any other sign of progression (i.e., new plasmacytoma, lytic bone lesion,
or hypercalcaemia)
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 0.261.65 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.