Consensus criteria for response and minimal residual disease (MRD) were published in 2016 , a decade after IMWG recommendations for the uniform reporting of clinical trials were first published . These new criteria, summarised in Table 25.4, define new minimal residual disease response categories (for patients who have achieved a complete response), that are based on flow cytometry, gene sequencing or imaging techniques. It is proposed that all future clinical trials in MM should follow these guidelines when reporting results.
Required baseline and follow-up tests for response assessment using IMWG consensus criteria
The κ/λ sFLC ratio is required for all patients to define a stringent CR. It should also be performed for all patients at suspected CR as well as at suspected clinical or biochemical progression. In addition, normalisation of sFLCs should also be performed at every time point (every cycle) for patients in whom the only measurable disease is by sFLC levels (Table 25.4).
The guidelines also discuss a potential role for Hevylite in the definition of MRD. Once patients are classified as IMWG MRD negative (by cell-based assays and imaging), normalisation of the Hevylite ratio may provide further evidence of tumour eradication and immune system recovery. Further study of Hevylite as a marker of MRD is encouraged.
|Stringent complete response (sCR)||CR as defined below, and|
|Complete response (CR)|
|Very good partial response (VGPR)|
|Partial response (PR)|
|Stable disease (SD)||Not meeting criteria for CR, VGPR, PR or progressive disease|
|Progressive disease (PD)||Any one or more of the following:
|*Subsequent evaluations can be used to further specify the duration of negativity (e.g. MRD-negative at 5 years)|
**Using EuroFlow standard operation procedure for MRD detection in MM, or validated equivalent method
***Presence of a clone defined as less than two identical sequencing reads obtained after DNA sequencing of bone marrow aspirates using the LymphoSIGHT platform or validated equivalent method
|Note that all response categories require two consecutive assessments made at any time before the institution of any new therapy; for MRD there is no need for two consecutive assessments, but information on MRD after each treatment stage is recommended. All categories of response and MRD require no known evidence of progressive or new bone lesions if radiographic studies were performed. Radiographic studies are not required to satisfy these response requirements. Bone marrow assessments need not be confirmed. For PD, serum M-protein increases of ≥10 g/L are sufficient to define relapse if baseline M-protein is ≥50 g/L.|
Table 25.4. IMWG criteria for response and MRD assessment in MM .
In patients with measurable disease by SPE or UPE (defined as serum monoclonal protein ≥10 g/L; urine monoclonal protein ≥200 mg/24 hours), or both, will be assessed for response based only on these two tests, and not by FLC assays. In these patients, FLC assays are only required for assessment of stringent complete response.
In patients in whom the only measurable disease is by sFLC levels (defined as involved FLC ≥100 mg/L, provided that the FLC ratio is abnormal), the definition of partial or very good partial sFLC response requires subtraction of the tumour ("involved") FLC from the non-tumour ("uninvolved") FLC. This difference calculation provides an interpretable result even when the non-tumour FLC is below the detection limit or fluctuating widely (thereby making the sFLC ratio unreliable). It is also helpful when interpreting high concentrations of the alternate FLC, as observed in patients with impaired renal function (Chapter 27).