Proposed response and relapse criteria for pPCL
| Response/relapse subcategory . | Criteria . |
|---|---|
| MRD-negative CR* | sCR as defined below plus |
| MRD-negative BM† by multicolor flow cytometry or allele-specific oligonucleotide PCR‡ and | |
| MRD-negative peripheral blood by multicolor flow cytometry or allele-specific oligonucleotide PCR‡ | |
| sCR* | CR as defined below plus |
| Normal FLC ratio and | |
| Absence of clonal cells in BM† by immunohistochemistry or immunofluorescence§ and | |
| Absence of clonal cells in peripheral blood by immunofluorescence | |
| CR* | Negative immunofixation on the serum and urine and |
| Disappearance of any soft tissue plasmacytomas and | |
| ≤ 5% plasma cells in BM† and | |
| No plasma cells in blood smear | |
| 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 per 24 h and |
| No plasma cells in blood smear | |
| PR* | ≥ 50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥ 90% or to < 200 mg per 24 h |
| If the serum and urine M-protein are immeasurable,‖ 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 immeasurable, and serum free light assay is also immeasurable, ≥ 50% reduction in BM plasma cells is required in place of M-protein, provided baseline BM plasma cell percentage was ≥ 30% | |
| In addition to the aforementioned criteria, a ≥ 90% reduction of peripheral blood plasma cells is required and peripheral blood plasma cells must be ≤ 5% of the differential white cell count, and if present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required | |
| SD* | Not meeting criteria for CR, VGPR, PR, or progressive disease |
| PD¶ (to be used for calculation of TTP and PFS endpoints for all patients, including those in CR (includes primary progressive disease and disease progression on or off therapy) | Progressive disease: requires any one or more of the following: |
| Increase of ≥ 25% from baseline/nadir in | |
| Serum M-component and/or (the absolute increase must be ≥ 0.5 g/dL)# | |
| Urine M-component and/or (the absolute increase must be ≥ 200 mg/24 h) | |
| Peripheral blood plasma cells (with at least 2 × 109 cells per L or > 20% of the differential white cell count) | |
| 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 | |
| BM plasma cell percentage: the absolute % must be ≥ 10%** | |
| 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 hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.65mM) that can be attributed solely to the plasma cell proliferative disorder | |
| Relapse from CR¶ (to be used only if the endpoint studied is DFS) | Any one or more of the following: |
| Reappearance of serum or urine M-protein by immunofixation or electrophoresis | |
| Reappearance of peripheral blood plasma cells in blood smear | |
| Development of ≥ 5% plasma cells in the BM** | |
| Appearance of any other sign of progression (ie, new plasmacytoma, lytic bone lesion, or hypercalcemia) |
| Response/relapse subcategory . | Criteria . |
|---|---|
| MRD-negative CR* | sCR as defined below plus |
| MRD-negative BM† by multicolor flow cytometry or allele-specific oligonucleotide PCR‡ and | |
| MRD-negative peripheral blood by multicolor flow cytometry or allele-specific oligonucleotide PCR‡ | |
| sCR* | CR as defined below plus |
| Normal FLC ratio and | |
| Absence of clonal cells in BM† by immunohistochemistry or immunofluorescence§ and | |
| Absence of clonal cells in peripheral blood by immunofluorescence | |
| CR* | Negative immunofixation on the serum and urine and |
| Disappearance of any soft tissue plasmacytomas and | |
| ≤ 5% plasma cells in BM† and | |
| No plasma cells in blood smear | |
| 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 per 24 h and |
| No plasma cells in blood smear | |
| PR* | ≥ 50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥ 90% or to < 200 mg per 24 h |
| If the serum and urine M-protein are immeasurable,‖ 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 immeasurable, and serum free light assay is also immeasurable, ≥ 50% reduction in BM plasma cells is required in place of M-protein, provided baseline BM plasma cell percentage was ≥ 30% | |
| In addition to the aforementioned criteria, a ≥ 90% reduction of peripheral blood plasma cells is required and peripheral blood plasma cells must be ≤ 5% of the differential white cell count, and if present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required | |
| SD* | Not meeting criteria for CR, VGPR, PR, or progressive disease |
| PD¶ (to be used for calculation of TTP and PFS endpoints for all patients, including those in CR (includes primary progressive disease and disease progression on or off therapy) | Progressive disease: requires any one or more of the following: |
| Increase of ≥ 25% from baseline/nadir in | |
| Serum M-component and/or (the absolute increase must be ≥ 0.5 g/dL)# | |
| Urine M-component and/or (the absolute increase must be ≥ 200 mg/24 h) | |
| Peripheral blood plasma cells (with at least 2 × 109 cells per L or > 20% of the differential white cell count) | |
| 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 | |
| BM plasma cell percentage: the absolute % must be ≥ 10%** | |
| 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 hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.65mM) that can be attributed solely to the plasma cell proliferative disorder | |
| Relapse from CR¶ (to be used only if the endpoint studied is DFS) | Any one or more of the following: |
| Reappearance of serum or urine M-protein by immunofixation or electrophoresis | |
| Reappearance of peripheral blood plasma cells in blood smear | |
| Development of ≥ 5% plasma cells in the BM** | |
| Appearance of any other sign of progression (ie, new plasmacytoma, lytic bone lesion, or hypercalcemia) |
Criteria are based on the International Myeloma Working Group (IMWG) criteria with some modifications and inclusion of the response subcategory MRD-negative CR.
MRD indicates minimal residual disease; FLC, free light chain; sCR, stringent complete response; SD, stable disease; PD, progressive disease; TTP, time to progression; and DFS, disease-free survival.
All response categories require 2 consecutive assessments made at any time before the institution of any new therapy; all categories also 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.
Confirmation with repeat BM biopsy is not needed.
Sensitivity attainable with 8-color multiparameter flow cytometry and allele-specific oligonucleotide PCR is 10−6.
The presence or absence of clonal cells is based on the κ/λ ratio. An abnormal κ/λ ratio by immunohistochemistry and/or immunofluorescence requires a minimum of 100 plasma cells for analysis. An abnormal ratio reflecting the presence of an abnormal clone is κ/λ of > 4:1 or < 1:2.
For measurable disease, serum M-protein ≥ 1 g/dL (≥ 10 g/L); urine M-protein ≥ 200 mg/24 h; involved FLC level ≥ 10 mg/dL (≥ 100 mg/L) provided serum FLC ratio is abnormal.
All relapse categories require 2 consecutive assessments made at any time before classification as relapse or disease progression and/or the institution of any new therapy.
For progressive disease, serum M-component increases of ≥ 1 g/dL (10 g/L) are sufficient to define relapse if starting M-component is ≥ 5 g/dL (50 g/L).
Relapse from CR has the 5% cut-off versus 10% for other categories of relapse.