Presenting Characteristics and Symptom Burden of Newly Diagnosed Older Multiple Myeloma Patients in the Commpass Study

Background: Multiple myeloma (MM) is a disease of older adults, with a median age of diagnosis in the late 60s.  While treatment advances have prolonged overall survival (OS) in MM, improvements have been modest among older MM patients.  Symptom burden and quality of life are concerns for older patients, as they are more susceptible to treatment intolerance and dose reduction or treatment cessation.  Older patients are often under-represented in clinical trials, and less information is available regarding their presenting clinical characteristics and treatment course.

The Multiple Myeloma Research Foundation (MMRF) CoMMpass study, is a multicenter study in newly diagnosed multiple myeloma.  It collects clinical-molecular data and patient reported health-related quality of life measures (EORTC QLQ-C30 and EORTC QLQ-MY20). In this study, we analyzed data from the CoMMpass study and compared presenting clinical characteristics, symptom burden and genetic features of newly diagnosed MM patients ≥ 75 years of age and those < 75 years of age.  An additional analysis of t(4;14) was performed among those aged <65 years, 65-75 years and > 75 years to confirm prior observations that the incidence of t(4;14) decreases with age (Avet-Loiseau et al. 2013).

Methods: Clinical data from the interim analysis 6 of the CoMMpass study was extracted via the MMRF Researcher Gateway.  CoMMpass eligibility requirements 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.  Enrollment began in July 2011.  Clinical data is recorded at enrolling centers by data analysts. Analysis was with STATA 12.0.  Categorical variables were compared with χ²; continuous variables were compared with student's t-tests and Wilcoxon rank-sum tests.

Results: 625 patients were eligible for analysis.   92 patients were ≥ 75 years of age, and 533 were < 75 years of age.  Median ages were 80 years (range 75-93) and 63 years (range 27-74).  Distribution of sex and race were evenly divided.  Older patients had higher rates of International staging system (ISS), stage III disease at presentation.  Baseline measurements of creatinine, platelet counts and hemoglobin were worse for older patients.  On symptom and quality of life assessment, older patients were more likely to have difficulties with physical functioning, and were less likely to have difficulties with emotional functioning or finances.  Subset analysis of those aged < 65 years, 65-75 years and > 75 years showed a trend towards decreasing rates of t(4;14). Results are summarized in Table 1.

Conclusion: Older patients in this study had higher ISS stage at diagnosis and worse ECOG performance status scores.  Baseline labs showed inferior renal function and lower platelet and hemoglobin levels.  Emotional and financial status was rated higher than younger patients, while physical functioning was worse.  A trend towards decreased incidence of t(4;14) was appreciated by age.

Table 1: Clinical Characteristics

	≥ 75 years (n=92)		< 75 years (n=533)	P
Demographics
Median age in years	80		63
Sex %				NS
Male	63		60
Female	37		40
Race %				NS
White	81		79
Black	19		18
Other	0		3
Heavy Chain %				NS
IgG	83		77
IgA	17		23
Light Chain %				NS
Kappa	65		62
Lambda	33		37
Biclonal	2		1
Disease Burden
ISS Stage %				<0.001
I		16	37
II		32	36
III		52	27
Serum M-Protein g/dL		2.96	2.8	NS
Bone Marrow % Plasma  Cells		9.6	8.6	NS
Calcium mmol/L		2.35	2.35	NS
Creatinine μmol/L		114.9	91.1	0.003
Hgb mmol/L		6.1	6.6	0.046
Platelets x109/L		191.5	216	0.001
LDH μkat/L		2.65	2.81	NS
Health-Related Symptoms/Quality of Life Measures
ECOG (%)				0.002
0		23	41
1		52	47
2		14	8
3-4		11	4
Global Health Scale		55.6	58.9	NS
Physical Functioning Scale		62.4	71.3	0.009
Social Functioning Scale		68.8	68.6	NS
Role Functioning Scale		58	60.6	NS
Emotional Functioning Scale		80.2	71.9	0.003
Cognitive Functioning Scale		77.2	80.9	NS
Financial Difficulties Scale		14.4	23.8	0.01
Fatigue Scale		40.3	38.2	NS
Pain Scale		39.3	41.1	NS
Molecular Characteristics (% of Patients)
Abnormal Cytogenetics		41	43	NS
del 13		31	29	NS
del 17		19	19	NS
t(11;14)		14.3	19.7	NS
t(4;14)		7	10.3	NS
Subset Analysis of t(4;14)		>75 years	65-75 years	<65 years	P
t(4;14) (% of patients)		5	7	13	0.053

 Median presented unless specified