Background: The clinical presentation of multiple myeloma (MM) varies greatly but often includes bone pain, anemia, renal dysfunction, hypercalcaemia, and/or constitutional symptoms. There are no signs or symptoms that are disease specific. The earliest staging system for MM, the Durie-Salmon (DS), associated disease and symptom burden with prognosis; however, it has been largely replaced by the International Staging System (ISS), which is easier to compute and better identifies patients with the poorest prognosis. It is unclear if ISS stage, like DS, is associated with disease or symptom burden.

Objective: To compare disease and symptom burden of patients with newly diagnosed MM by ISS Stage.

Methods: Data was extracted from the open-access Multiple Myeloma Research Foundation (MMRF) Researcher Gateway corresponding with interim analysis 6 from the CoMMpass study. The CoMMpass study is enrolling 1000 newly diagnosed MM patients who will be tracked longitudinally for 5 years. CoMMpass collects relevant clinical data and patient reported quality of life (EORTC QLQ-C30 and QLQ-MY20), as well as sequential tissue samples. Eligibility requirements for CoMMpass include: symptomatic MM with measureable disease by SPEP (≥1.0g/dL), UPEP (≥200mg/24 hours), or SFLC (≥10mg/dL); receiving an immunomodulator and/or a proteasome inhibitor for initial MM treatment; and no prior malignancies in the past 5 years.

All clinical data was reported by trained data analysts at the enrolling center with the exception of flow cytometry which was performed centrally; raw lab values for beta-2 microglobulin and albumin were entered and stage was subsequently calculated by the analysts for this study according to the ISS (Greipp et al, JCO 2005). Twenty-six patients with unknown ISS were excluded from the analysis. Data was analyzed using SPSS 21. Categorical variables were compared using χ2, continuous with one-way ANOVA tests.

Results: 599 patients were eligible for analysis. Sex, race, and heavy and light chain isotypes were all evenly distributed among the ISS stages; however, median age for ISS stage III was 67, 65 for stage II and 62 for stage I (p<0.001). Stage I and II patients were similar in disease burden, but stage III patients had higher serum M-proteins (p<0.001), LDH (p=0.002), bone marrow plasma cells (p<0.001), circulating plasma cells (p<0.001), and creatinine (p<0.001), and lower hemoglobin (p<0.001) and platelets (p=0.001). Further, stage III patients had poorer performance status (p<0.001), global health (p<0.001), physical functioning (p<0.001), social functioning (p<0.001), and role functioning (p<0.001), and increased fatigue (p<0.001) and pain (p=0.016). Results are summarized in Table 1.

Conclusions: Stage III had a higher disease and symptom burden than stage I and II patients. Stage I and II patients were similar in most measures suggesting that ISS may not discriminate between these groups well, this is supported by other studies that have failed to find outcomes differences between stage I and II patients.

Table 1.
Stage I
n= 204		Stage II
n = 210		Stage III
n = 185		p
Demographics 
Age in years  62 65 67 <0.001 
Male  64% 57% 62% NS 
Race     NS 
White 80% 83% 74%  
Black 19% 13% 23%  
Other 2% 3% 3%  
Heavy Chain    NS 
IgG 80% 80% 75%  
IgA 20% 20% 25%  
Light Chain    NS 
Kappa 65% 61% 60%  
Lambda 34% 38% 38%  
Biclonal 1% 2% 2%  
Disease Burden 
Serum M-Protein g/dL  1.9 2.0 3.2 <0.001 
LDH μkat/L  2.7 2.8 3.0 0.002 
Bone Marrow Plasma Cells* 7% 9% 13% <0.001 
Circulating Plasma Cells*  0% 0% 0.1% <0.001 
Calcium mmol/L 2.4 2.3 2.4 <0.001 
Creatinine μmol/L 82 88 149 <0.001 
Hgb mmol/L 7.4 6.4 5.8 <0.001 
Platelets x109/L  222 212 199 .001 
Bone Lesions 61% 52% 53% NS 
Symptom Burden/Quality of Life Measures 
ECOG Performance Status     <0.001 
0 47% 42% 22%  
1 49% 42% 54%  
2 5% 8% 15%  
3-4 0% 8% 9%  
Global Health Scale 66 66 50 <0.001 
Physical Functioning Scale 86 80 63 <0.001 
Cognitive Functioning Scale 83 83 83 NS 
Emotional Functioning Scale 75 75 75 NS 
Social Functioning Scale 83 83 66 <0.001 
Role Functioning Scale 66 66 50 <0.001 
Disease Symptom Scale 27  22 27 NS 
Fatigue Scale 33 33 44 <0.001 
Pain Scale 33 33 42 0.016 
Stage I
n= 204		Stage II
n = 210		Stage III
n = 185		p
Demographics 
Age in years  62 65 67 <0.001 
Male  64% 57% 62% NS 
Race     NS 
White 80% 83% 74%  
Black 19% 13% 23%  
Other 2% 3% 3%  
Heavy Chain    NS 
IgG 80% 80% 75%  
IgA 20% 20% 25%  
Light Chain    NS 
Kappa 65% 61% 60%  
Lambda 34% 38% 38%  
Biclonal 1% 2% 2%  
Disease Burden 
Serum M-Protein g/dL  1.9 2.0 3.2 <0.001 
LDH μkat/L  2.7 2.8 3.0 0.002 
Bone Marrow Plasma Cells* 7% 9% 13% <0.001 
Circulating Plasma Cells*  0% 0% 0.1% <0.001 
Calcium mmol/L 2.4 2.3 2.4 <0.001 
Creatinine μmol/L 82 88 149 <0.001 
Hgb mmol/L 7.4 6.4 5.8 <0.001 
Platelets x109/L  222 212 199 .001 
Bone Lesions 61% 52% 53% NS 
Symptom Burden/Quality of Life Measures 
ECOG Performance Status     <0.001 
0 47% 42% 22%  
1 49% 42% 54%  
2 5% 8% 15%  
3-4 0% 8% 9%  
Global Health Scale 66 66 50 <0.001 
Physical Functioning Scale 86 80 63 <0.001 
Cognitive Functioning Scale 83 83 83 NS 
Emotional Functioning Scale 75 75 75 NS 
Social Functioning Scale 83 83 66 <0.001 
Role Functioning Scale 66 66 50 <0.001 
Disease Symptom Scale 27  22 27 NS 
Fatigue Scale 33 33 44 <0.001 
Pain Scale 33 33 42 0.016 

Note-Median presented unless specified.

*- CD38+/CD138+ by flow cytometry

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Disclosures

Vij:Takeda, Onyx: Research Funding; Celgene, Onyx, Takeda, Novartis, BMS, Sanofi, Janssen, Merck: Consultancy.

Topics:
multiple myeloma, antigens, cd98 light chains, creatinine, fatigue, flow cytometry, hemoglobin, albumins, anemia, beta 2-microglobulin, bone lesion

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2015 by The American Society of Hematology
2015
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