Monitoring
Treatment response
should be evaluated after every therapy cycle.
Please
see Response Assessment
under Monitoring
for further information.
The recommended
laboratory tests during follow-up or surveillance include CBC with differential
and platelet count, serum creatinine level, calcium level, serum and urine
M-protein level, and Ig studies.
The following tests may be considered as clinically indicated:
- Serum quantitative immunoglobulins, SPEP and SIFE
- 24-hour urine for total protein, UPEP and UIFE at baseline, as clinically indicated in patients’ post-primary treatment, as needed post- hematopoietic cell transplantation, or if with significant change in FLC levels
- Serum FLC assay: Should be obtained every 2-3 months or as clinically indicated
- Imaging modalities (eg whole body MRI without contrast, WBLD-CT, whole-body FDG PET/ CT): To be done annually after primary treatment or as clinically indicated; test done at diagnosis is preferred
- Skeletal survey may be done in certain circumstances
- Bone marrow aspirate and biopsy with multiparameter flow cytometry as clinically indicated after primary treatment or as needed after hematopoietic cell transplantation
- Minimal residue disease (MRD) assessment
Patients receiving Carfilzomib should be closely
monitored for any cardiac or lung toxicities. The occurrence of new bone
lesions should be monitored using patient history and imaging modalities (eg
skeletal radiography, MRI, WBLD-CT, PET-CT). Follow-up bone imaging may be
considered if disease progression is suspected.
Response Assessment
The assessment of
clinical response is recommended after every treatment cycle.
International Myeloma Working Group (IMWG) Criteria for Response
Assessment
| Category | Criteria |
| IMWG Minimal Residual Disease (MRD) Criteria | |
| Sustained MRD-negative | No MRD in the marrow as defined by next-generation flow (NGF), next-generation sequencing (NGS), or both, and in imaging*, within a minimum span of 1 year apart. Specific duration of negativity to be based on subsequent evaluations |
| Flow MRD-negative | Phenotypically aberrant clonal plasma cells by NGF absent in bone marrow aspirate using the EuroFlow standard operating procedure for MRD detection in multiple myeloma with sensitivity of ≥1 in 105 nucleated cells |
| Sequencing MRD-negative | Clonal plasma cells by NGS absent in bone marrow aspirate; clone present defined as <2 identical sequencing reads obtained after DNA sequencing of bone marrow aspirates by a validated equivalent methods with sensitivity of ≥1 in 105 nucleated cells |
| Imaging plus MRD-negative | MRD-negative as defined by NGF or NGS, plus complete disappearance, decreased to less mediastinal blood pool standardized uptake values (SUV), or decreased to less than that of the surrounding normal tissue, of tracer in previous areas identified with increased tracer uptake at baseline or preceding PET/CT |
| Standard IMWG Response Criteria | |
| Complete response | Negative serum and urine immunofixation without any soft tissue plasmacytomas and <5% plasma cells in bone marrow aspirates |
| Stringent complete response | Complete response plus normal FLC ratio◊ and negative clonal cells in bone marrow biopsy by immunohistochemistry (κ/λ ratio ≤4:1 for κ or ≥1:2 for λ patients after counting ≥100 plasma cells) |
| Very good partial response | Serum and urine M-protein detectable by immunofixation but not on serum protein electrophoresis (SPEP), or ≥90% reduction in serum M-protein with urine M-protein <100 mg/24 hours |
| Partial response | Serum M-protein reduced by ≥50%, plus ≥90% reduction of 24-hour urinary M-protein, or <200 mg/24 hours urinary M-protein
Or ≥50% reduction in plasma cells (in place of M-protein) if with baseline BMPC percentage of ≥30% plus ≥50% reduction in size of soft tissue plasmacytomas if obtained at baseline |
| Minimal response | ≥25% but ≤49% reduction in serum M-protein and 50-89% reduced 24-hour urine M-protein or 25-49% reduction in size of soft tissue plasmacytomas if obtained at baseline |
| Stable disease | Does not meet the criteria for complete response, very good partial response, partial response, minimal response, or progressive disease Not recommended to be used as an indicator of response |
| Progressive disease |
25% increase from lowest confirmed response value in ≥1 of the following:
|
| Clinical relapse |
≥1 of the following:
|
| Relapse from complete response# |
≥1 of the following:
|
| Relapse from MRD-negative# |
≥1 of the following:
|
*Negative imaging results defined as complete disappearance, decreased to less mediastinal blood pool SUV or decreased to less than that of the surrounding normal tissue, of tracer in previous areas identified with increased tracer uptake at baseline or preceding PET/CT.
◊Validated by Freelite test.
†Sum of the products of the maximal perpendicular diameters of measured lesions.
#If endpoint is disease-free survival.