Response criteria and disease status
The effect or response to treatment is generally based on a measure of the bulk of myeloma, determined by changes in:
- Paraprotein and serum free light chain (sFLC) levels
- Percentage of plasma cells in bone marrow
- Presence of plasmacytomas, lytic lesions or other symptoms
In the past, different treatment response criteria developed by different organisations in Europe (European Society for Blood and Marrow Transplantation, EBMT) and the USA (Eastern Cooperative Oncology Group, ECOG; South West Oncology Group, SWOG) were used but this meant that the results of international studies could not be directly compared.
The IMWG uniform response criteria have been the standard criteria used to determine a patient’s response to treatment. Measuring response to treatment not only determines how well the myeloma is being controlled but also provides prognostic information since the depth of response is associated with survival outcome.
Traditionally, treatment response has been assessed by measuring serum and urine paraprotein levels using protein electrophoresis and immunofixation and by quantifying the percentage of bone marrow plasma cells from a trephine biopsy. Later, the criteria were updated to include SFLC measurement and calculation of the free light chain ratio.
Treatments for myeloma have radically improved outcomes especially since the introduction of more targeted drugs with different mechanisms of action. These have led to improved rates and depths of response, with more and more patients achieving a complete response (CR).
As complete response rates have improved, more rigorous definitions to describe the various responses have been developed, which are summarised in the table below.
Definitions of treatment response in myeloma
| Response category | Response criteria |
|---|---|
| Stringent complete response (sCR) | Meets all the criteria for complete response and normal serum FLC ratio and absence of bone marrow clonal cells by immunohistochemistry |
| Complete response (CR) | Disappearance of all evidence of serum and urine M proteins on immunofixation and ≤ 5% bone marrow plasma cells and disappearance of any soft tissue plasmacytomas |
| Very good partial response (VGPR) | Meets all criteria for partial response and Serum and urine M proteins detectable by immunofixation but not by electrophoresis or ≥ 90% reduction in serum M protein plus urinary M protein < 100mg/24 hrs |
| Partial response (PR) | ≥ 50% reduction in serum M protein plus reduction in 24 hr urinary M protein by ≥ 90% or to < 200mg per 24 hrs If serum and urinary M proteins are unmeasurable, a ≥ 50% decrease in the difference between involved and uninvolved FLC levels is required instead of M protein criteria If serum and urinary M protein, and FLCs are unmeasurable, ≥ 50% reduction in plasma cells is required provided baseline % was ≥ 30% If present at baseline, a ≥ 50% reduction in size of soft tissue plasmacytomas |
| Minimal response | ≥ 25% but ≤ 49% reduction of serum M protein and reduction in urinary M protein by 50 -89% |
| Stable disease | Does not meet criteria for sCR, CR, VGPR, PR or progression |
| Progressive disease | > 25% increase in blood or urine paraprotein, or development of new myeloma symptoms, or new bone damage seen on scans |
FLC, free light chain