ASCO GUIDELINES Bundle

14 Table 5. IMWG Response Criteria Response IMWG criteria 1 Relapse Clinical relapse requires one or more of: Direct indicators of increasing disease and/or end organ dysfunction (CRAB features). 5 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 • Development of new soft tissue plasmacytomas or bone lesions • 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 • Hypercalcemia (>11.5 mg/dL) [2.65 mmol/L] • Decrease in haemoglobin of ≥2 g/dL [1.25 mmol/L] • Rise in serum creatinine by 2 mg/dL or more [177 mmol/L or more] Relapse from CR 4 (To be used only if the end point studied is DFS) 7 Any one or more of the following : • Reappearance of serum or urine M-protein by immunofixation or electrophoresis • Development of ≥5% plasma cells in the bone marrow 6 • Appearance of any other sign of progression (i.e., new plasmacytoma, lytic bone lesion, or hypercalcaemia) Note: Adapted from the International Myeloma Working Group website. Accessed on October 9, 2018 1 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. 2 Confirmation with repeat bone marrow biopsy not needed. 3 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. 4 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. e definitions of relapse, clinical relapse and relapse from CR are not to be used in calculation of time to progression or progression-free survival. 5 For progressive disease, serum M-component increases of ≥1 gm/dL are sufficient to define relapse if starting M-component is ≥5 g/dL. 6 Relapse from CR has the 5% cut-off versus 10% for other categories of relapse. 7 For purposes of calculating time to progression and progression-free survival, CR patients should also be evaluated using criteria listed above for progressive disease. Treatment

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