Multiples Myelom

CR complete Response

• Negative immunofixation on the serum and urine

  • Absence of the original monoclonal paraprotein in serum and urine by immunofixation, maintained for a minimum of 6 weeks. The presence of oligoclonal bands consistent with oligoclonal immune reconstitution does not exclude CR

• Disappearance of any soft tissue plasmacytoma

• <5% bone marrow plasma cells

  • < 5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy, if biopsy is performed. If absence of monoclonal protein is sustained for 6 weeks it is not necessary to repeat the bone marrow, except in patients with non-secretory myeloma where the marrow examination must be repeated after an interval of at least 6 weeks to confirm CR.
    
    

• normal FLC ratio
  

  • in patients for whom only measurable disease is by serum FLC level, normal FLC ratio of 0.26 to 1.65 in addition to CR criteria is required; two consecutive assessments are needed

sCR stringent complete response - CR as defined above plus

• Normal SFLC ratio
  

• Absence of phenotypically aberrant plasma cells by multiparameter flow cytometry

Immunophenotypic CR

• sCR as defined plus absence of phenotypically aberrant plasma cells (clonal) in bone marrow with minimum of 1 million total bone marrow cells analyzed by multiparametric flow cytometry (with  four colors)

Molecular CR

• sCR as defined plus negative allele-specific oligonucleotide polymerase chain reaction (sensitivity 105)

Very good partial response (VGPR)

• Serum and urine M-protein detectable by immunofixation but not on electrophoresis
  
  OR
  
  

• >90% reduction in serum M-protein plus reduction in 24-h urinary M-protein by> 90% or to <100mg/24 h

  • in patients for whom only measurable disease is by serum FLC level, > 90% decrease in difference between involved and uninvolved FLC levels, in addition to VGPR criteria, is required; two consecutive assessments are needed

Partial response (PR)

• >50% reduction of serum M-protein and reduction in 24-h urinary M-protein by>90% or to <200mg/24 h maintained for 6 weeks

  • If serum and urine M protein are not measurable, > 50% decrease in difference between involved and uninvolved FLC levels is required in place of M protein criteria
    
    If serum and urine M protein and serum FLC assay are not measurable, > 50% reduction in bone marrow plasma cells is required in place of M protein, provided baseline percentage was > 30%
    
    In addition, if present at baseline, > 50% reduction in size of soft tissue plasmacytomas is required
    
    Two consecutive assessments are needed; no known evidence of progressive or new bone lesions if radiographic studies were performed.

MR for relapsed refractory myeloma only

• >25% but < 49% reduction of serum M protein and reduction in 24-hour urine M protein by 50% to 89%

• In addition, if present at baseline, 25% to 49% reduction in size of soft tissue plasmacytomas is also required No increase in size or number of lytic bone lesions (development of compression fracture does not exclude response)

Stable disease (SD)

• Not meeting criteria for CR, VGPR, PR, or PD; no known evidence of progressive or new bone lesions if radiographic studies were performed

Progressive disease (PD)

• Increase of 25% from lowest response value in any of following:

• Serum M component with absolute increase > 0.5 g/dL; serum M component increases> 1 g/dL are sufficient to define relapse if starting M component is >= 5 g/dL and/or;
  
  Urine M component (absolute increase must be >= 200 mg/24 h) and/or;
  
  Only in patients without measurable serum and urine M protein levels: difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL)

Development of new or definite increase in size of existing bone lesions or soft tissue plasmacytomas Development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder

Two consecutive assessments before new therapy are needed

Development of hypercalcaemia (corrected serum calcium >11·5 mg/dl or 2·8 mmol/l) not attributable to any other cause.

Relaps from CR

• Reappearance of serum or urinary paraprotein on immunofixation or routine electrophoresis, confirmed by at least one further investigation and excluding oligoclonal immune reconstitution.
• >5% plasma cells in a bone marrow aspirate or on trephine bone biopsy.
• Development of new lytic bone lesions or soft tissue plasmacytomas or definite increase in the size of residual bone lesions (development of a compression fracture does not exclude continued response and may not indicate progression).
• Development of hypercalcaemia (corrected serum calcium >11·5 mg/dl or 2·8 mmol/l) not attributable to any other cause.