Abstract
Although management of multiple myeloma has changed substantially in the last decade, it is unknown whether the burden of ESRD due to multiple myeloma has changed, or whether survival of patients with multiple myeloma on RRT has improved. Regarding ESRD due to multiple myeloma necessitating RRT in the United States, we evaluated temporal trends between 2001 and 2010 for demography-adjusted incidence ratios, relative to rates in 2001–2002, and mortality hazards from RRT initiation, relative to hazards in 2001–2002. In this retrospective cohort study, we used the US Renal Data System database (n=1,069,343), 2001–2010, to identify patients with ESRD due to multiple myeloma treated with RRT (n=12,703). Demography-adjusted incidence ratios of ESRD from multiple myeloma decreased between 2001–2002 and 2009–2010 in the overall population (demography-adjusted incidence ratio 0.82; 95% confidence interval, 0.79 to 0.86) and in most demographic subgroups examined. Mortality rates were 86.7, 41.4, and 34.4 per 100 person-years in the first 3 years of RRT, respectively, compared with 32.3, 20.6, and 21.3 in matched controls without multiple myeloma. Unadjusted mortality hazards ratios declined monotonically after 2004 to a value of 0.72; 95% confidence interval, 0.67 to 0.77 in 2009–2010, and declines between 2001–2002 and 2008–2009 were observed (P<0.05) in most demographic subgroups examined. Findings were similar when adjustment was made for demographic characteristics, comorbidity markers, and laboratory test values. These data suggest the incidence of RRT from multiple myeloma in the United States has decreased in the last decade, and clinically meaningful increases in survival have occurred for these patients.
Keywords: PI3K, vesicular trafficking, cystic kidney, polycystins, primary cilium, proliferation
ESRD is a feared complication of multiple myeloma, which is reported to be the most common malignancy leading to ESRD.1 In this regard, the therapeutic approach to earlier-stage multiple myeloma has changed substantially in recent decades.2–11 However, the current belief is that even with aggressive therapy, the risk of progression to ESRD is high, recovery of renal function is low, and survival time on dialysis therapy is very short.12 As the detection and treatment of multiple myeloma continues to evolve, it seems natural to question whether reductions in associated ESRD have occurred, and if so, among which demographic subgroups. Surprisingly few, if any, national-level clinical epidemiologic studies of ESRD due to multiple myeloma are available. Hence, we describe the clinical epidemiology of ESRD due to multiple myeloma in the United States between 2001 and 2010.
Results
A total of 12,703 patients initiated RRT due to multiple myeloma between 2001 and 2010 (Table 1), yielding a rate of 4.3 cases per million per year (PMPY). Among subgroups, rates exceeding the overall estimate were observed in groups characterized by year of initiation (2001–2002 [2557 cases; 4.5 PMPY] and 2005–2006 [2696 cases; 4.6 PMPY]), age ≥65 years (8083 cases; 10.8 PMPY), and black ethnicity/race (2641 cases; 6.3 PMPY). The demography-adjusted incidence ratio (AIR) for ESRD due to multiple myeloma was lower for patients aged <40 years (0.06; 95% confidence interval [95% CI], 0.06 to 0.07 versus 40–64 years) and of other ethnicity/race (0.77; 95% CI, 0.71 to 0.83 versus white). The AIR was higher for patients aged ≥65 years (4.99; 95% CI, 4.86 to 5.12 versus 40–64 years), of male sex (1.6; 95% CI, 1.56 to 1.64 versus female), and of non-Hispanic black ethnicity/race (2.45; 95% CI, 2.37 to 2.52 versus white). The AIR decreased (P<0.05) between 2001–2002 and 2009–2010 in the overall population (0.82; 95% CI, 0.79 to 0.86) and in all subgroups examined, except age <40 years, and Hispanic and other ethnicity/race.
Table 1.
Incidence ratios of ESRD due to multiple myeloma requiring RRT, 2001–2010
| Analysis of the Overall Population | Standardized Incidence Ratios within Subgroups (versus 2001–2002) | ||||||
|---|---|---|---|---|---|---|---|
| Incidence Ratios | |||||||
| Cases/Rate (PMPY) | Crude | Standardized | 2003–2004 | 2005–2006 | 2007–2008 | 2009–2010 | |
| All | 12,703 (4.3) | — | — | 0.96 (0.92–0.99)b | 0.99 (0.95–1.03)a | 0.89 (0.86–0.92) | 0.82 (0.79–0.86) |
| 2001–2002 | 2557 (4.5) | 1 (Reference) | 1 (Reference) | — | — | — | — |
| 2003–2004 | 2517 (4.3) | 0.99 (0.95–1.03)a | 0.96 (0.92–0.99)b | — | — | — | — |
| 2005–2006 | 2696 (4.6) | 0.99 (0.96–1.03)a | 0.99 (0.95–1.03)a | — | — | — | — |
| 2007–2008 | 2512 (4.2) | 0.93 (0.89–0.97) | 0.89 (0.86–0.92) | — | — | — | — |
| 2009–2010 | 2421 (3.9) | 0.85 (0.82–0.88) | 0.82 (0.79–0.86) | — | — | — | — |
| Age <40 | 172 (0.1) | 0.06 (0.06–0.07) | 0.06 (0.05–0.07) | 1.08 (0.74–1.58)a | 1.36 (0.96–1.93)a | 1.44 (1.01–2.04)b | 1.28 (0.89–1.82)a |
| Age 40–64 | 4448 (2.3) | 1 (Reference) | 1 (Reference) | 1.03 (0.96–1.1)a | 1.11 (1.04–1.18)c | 0.97 (0.91–1.04)a | 0.93 (0.87–1)b |
| Age ≥65 | 8083 (10.8) | 4.65 (4.53–4.77) | 4.99 (4.86–5.12) | 0.92 (0.87–0.96) | 0.93 (0.88–0.97)c | 0.84 (0.8–0.88) | 0.76 (0.73–0.8) |
| Male | 7139 (3.5) | 1.18 (1.15–1.2) | 1.6 (1.56–1.64) | 0.95 (0.9–1)a | 1.04 (0.99–1.1)a | 0.99 (0.94–1.04)a | 0.89 (0.85–0.94) |
| Female | 5564 (3) | 1 (Reference) | 1 (Reference) | 0.96 (0.91–1.02)a | 0.93 (0.88–0.99)b | 0.78 (0.73–0.82) | 0.74 (0.7–0.79) |
| White | 9703 (2.9) | 1 (Reference) | 1 (Reference) | 0.95 (0.91–1)b | 1 (0.96–1.05)a | 0.91 (0.87–0.95) | 0.83 (0.79–0.87) |
| Black | 2641 (6.3) | 2.15 (2.08–2.21) | 2.45 (2.37–2.52) | 0.97 (0.89–1.05)a | 1 (0.92–1.09)a | 0.85 (0.78–0.93) | 0.83 (0.76–0.9) |
| Other | 359 (2.5) | 0.83 (0.77–0.9) | 0.77 (0.71–0.83) | 0.89 (0.71–1.11)a | 0.61 (0.48–0.78) | 0.69 (0.55–0.86)c | 0.57 (0.46–0.72) |
Parameter estimates are rates PMPY or incidence ratios with standard errors with 95% confidence intervals in parentheses. Adjustment factors included age, sex, and race-ethnicity. P<0.001 unless otherwise indicated. Reference indicates the group used for statistical comparisons.
P≥0.05.
0.01≤P<0.05.
0.001≤P<0.01.
Table 2 shows baseline characteristics of patients with multiple myeloma requiring RRT at dialysis initiation compared with characteristics of patients with ESRD due to all other causes. More patients with multiple myeloma were aged ≥65 years (63.6% versus 48.9%), white (76.4% versus 65.4%), and non-Hispanic (93.6% versus 86.5%). After adjustment for baseline demographics, characteristics associated with multiple myeloma as cause of ESRD included: older age; non-Hispanic ethnicity; lack of ischemic heart disease and diabetes; hemodialysis for RRT; vascular access other than fistula for hemodialysis; shorter duration of nephrologist care; and lower eGFR, body mass index, serum albumin, and hemoglobin levels. Adjusted odds ratios (AOR) for multiple myeloma as cause of ESRD were notably higher for groups characterized by age ≥65 years (AOR, 1.35; 95% CI, 1.3 to 1.41 versus 40–64 years), use of graft (1.67; 95% CI, 1.33 to 2.1 versus fistula) or catheter (AOR, 4.68; 95% CI, 4.12 to 5.31 versus fistula) for hemodialysis, and nephrologist care for <12 months (AOR, 3.29; 95% CI, 3.04 to 3.56 versus >12 months). AOR estimates were notably lower for groups characterized by age <40 years (AOR, 0.19; 95% CI, 0.17 to 0.23 versus 40–64 years), black race (AOR, 0.63; 95% CI, 0.61 to 0.66 versus white), other race (AOR, 0.41; 95% CI, 0.37 to 0.46 versus white), Hispanic ethnicity (AOR, 0.42; 95% CI, 0.39 to 0.46 versus non-Hispanic), presence of ischemic heart disease (AOR, 0.39; 95% CI, 0.37 to 0.41 versus absent) or diabetes (AOR, 0.19; 95% CI, 0.18 to 0.2 versus absent), use of peritoneal dialysis as primary modality (AOR, 0.47; 95% CI, 0.42 to 0.52 versus hemodialysis), and eGFR >15 ml/min per 1.73 m2 (AOR, 0.39; 95% CI, 0.37 to 0.42 versus ≤15 ml/min per 1.73 m2).
Table 2.
Baseline characteristics at initiation (n=1,069,343)
| Cause of ESRD | Multiple Myeloma | AOR, Multiple Myeloma | |
|---|---|---|---|
| Yes | No | ||
| N | 12,703 | 1,056,640 | |
| Age, years | |||
| <40 | 1.4 | 9.2 | 0.19 (0.17–0.23) |
| 40–64 | 35 | 41.9 | 1 (Reference) |
| ≥65 | 63.6 | 48.9 | 1.35 (1.3–1.41) |
| Sex | |||
| Men | 56.2 | 55.6a | 1 (Reference)a |
| Women | 43.8 | 44.4 | 0.99 (0.95–1.02) |
| Race | |||
| White | 76.4 | 65.4 | 1 (Reference) |
| Black | 20.8 | 28.5 | 0.63 (0.61–0.66) |
| Other | 2.8 | 6.1 | 0.41 (0.37–0.46) |
| Ethnicity | |||
| Hispanic | 6.4 | 13.6 | 0.42 (0.39–0.46) |
| Non-Hispanic | 93.6 | 86.5 | 1 (Reference) |
| Ischemic heart disease | |||
| No | 86.1 | 76.3 | 1 (Reference) |
| Yes | 13.9 | 23.7 | 0.39 (0.37–0.41) |
| Diabetes | |||
| No | 82.5 | 47.7 | 1 (Reference) |
| Yes | 17.5 | 52.3 | 0.19 (0.18–0.2) |
| Mode of RRT | |||
| Hemodialysis | 96.9 | 91.4 | 1 (Reference) |
| Peritoneal dialysis | 3.1 | 6.6 | 0.47 (0.42–0.52) |
| Initial vascular access (hemodialysis) | |||
| Fistula | 3.6 | 13.9 | 1 (Reference) |
| Graft | 1.5 | 3.6 | 1.67 (1.33–2.1) |
| Catheter | 94.9 | 82.4 | 4.68 (4.12–5.31) |
| Nephrologist care, months | |||
| >12 | 9.6 | 24.4 | 1 (Reference) |
| ≤12 | 90.4 | 75.6 | 3.29 (3.04–3.56) |
| eGFR, ml/min per 1.73 m2 | |||
| ≤15 | 94.3 | 87.4 | 1 (Reference) |
| >15 | 5.7 | 12.6 | 0.39 (0.37–0.42) |
| BMI, kg/m2 | |||
| <30 | 78.7 | 66.3 | 1 (Reference) |
| ≥30 | 21.3 | 33.7 | 0.53 (0.51–0.56) |
| Albumin, g/dl | |||
| ≥3.5 | 28.8 | 35 | 1 (Reference) |
| <3.5 | 71.2 | 65 | 1.35 (1.29–1.41) |
| Hemoglobin, g/dl | |||
| <9 | 36.3 | 25.6 | 1 (Reference) |
| ≥9 | 63.7 | 74.4 | 0.52 (0.5–0.54) |
Parameter estimates are presented as column percentages or odds ratios, with 95% confidence intervals in parentheses. As data fields for pre-dialysis vascular access for hemodialysis and nephrologist care before RRT were not available before the 2005 version of the Medical Evidence Report, these variables are provided for 59.1% of the study population. Missing data: initial hemodialysis access, 46.6%; prior nephrology care, 40.9%; eGFR, 0.6%; BMI, 1.4%; serum albumin, 24.5%; hemoglobin, 8.3%. P<0.001 unless otherwise indicated for comparisons of patients with and without multiple myeloma. BMI, body mass index; AOR, adjusted odds ratio (with logistic regression and age, sex, race, and ethnicity as adjustment factors).
P≥0.05.
Patients with multiple myeloma as the cause of ESRD were more likely to die during their follow-up period; a total of 86.6% died (mean follow-up period, 1.6 years), compared with 62.1% of those with ESRD due to other causes (mean follow-up period, 3.4 years; P<0.001). Survival after initiation of RRT for patients with ESRD due to multiple myeloma was significantly worse than for patients with ESRD due to other causes at initiation (Figure 1).
Figure 1.
Survival curves with 95% confidence limits in patients with ESRD due to multiple myeloma (n=12,702, black curve) versus ESRD due to other causes (gray curve) at initiation of maintenance RRT (P<0.001).
Causes of death were distributed differently for patients with and without multiple myeloma (P<0.001). In patients with multiple myeloma, the top reported causes of death (versus patients without multiple myeloma) were malignant disease (34.3% versus 2.8%), cardiac arrest (18.5% versus 29.1%), infection (8.3% versus 6.6%), and withdrawal of RRT (8.2% versus 9.7%). Mortality rates in patients with multiple myeloma (Figure 2) were 86.7, 41.4, and 34.4 per 100 person-years in the first 3 years of RRT, compared with 32.3, 20.6, and 21.3, respectively, in matched controls without multiple myeloma; mortality rates were higher, reaching statistical significance, in patients with multiple myeloma (P<0.05) in each year and subgroup studied, except age <40 years in years 2 and 3 and Hispanic ethnicity in year 3.
Figure 2.
Mortality rates in the first 3 years of RRT in patients with multiple myeloma (MM+) and a matched control group (MM-). Error bars are 95% confidence intervals. Patients were matched by age, sex, race, ethnicity, and year of RRT inception. Matching occurred for 12,654 of 12,703 patients with multiple myeloma (99.6%). Subgroups are reported by year of RRT initiation (five 2-year periods), age (three levels), sex, and race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic, and other). AA, African American; RE, race/ethnicity.
Table 3 shows mortality hazard ratios for different years of RRT initiation in patients with multiple myeloma, with 2001 and 2002 as reference category. Unadjusted hazards ratios (Table 3, Model 1) declined monotonically after 2004 to a value of 0.72; 95% CI, 0.67 to 0.77 in 2009–2010, and declines between 2001–2002 and 2008–2009 were observed (P<0.05) in all demographic subgroups examined, except age <40 years and Hispanic ethnicity. Findings were similar when adjustment was made for demographic characteristics (Table 3, model 2) or demographic characteristics, comorbidity markers, and laboratory test values (model 3).
Table 3.
Hazards ratios for death by year of RRT inception, for patients with multiple myeloma (n=12,702)
| Year | ||||||||
|---|---|---|---|---|---|---|---|---|
| 2003–2004 | 2005–2006 | 2007–2008 | 2009–2010 | |||||
| Hazards Ratio (95% CI) | P value | Hazards Ratio (95% CI) | P value | Hazards Ratio (95% CI) | P value | Hazards Ratio (95% CI) | P value | |
| Model 1 | ||||||||
| All | 0.99 (0.93 to 1.06) | 0.9 | 0.89 (0.83 to 0.95) | 0.001 | 0.83 (0.77 to 0.89) | <0.001 | 0.72 (0.67 to 0.77) | <0.001 |
| Age, years | ||||||||
| <40 | 0.66 (0.32 to 1.36) | 0.3 | 0.39 (0.18 to 0.84) | 0.02 | 0.69 (0.34 to 1.39) | 0.3 | 0.79 (0.36 to 1.71) | 0.5 |
| 40–64 | 1.04 (0.92 to 1.18) | 0.5 | 0.94 (0.83 to 1.06) | 0.3 | 0.81 (0.71 to 0.92) | 0.001 | 0.74 (0.64 to 0.85) | <0.001 |
| ≥65 | 1 (0.92 to 1.09) | 0.9 | 0.92 (0.85 to 1) | 0.04 | 0.86 (0.79 to 0.94) | <0.001 | 0.73 (0.67 to 0.8) | <0.001 |
| Sex | ||||||||
| Men | 1.03 (0.94 to 1.13) | 0.5 | 0.91 (0.83 to 1) | 0.04 | 0.86 (0.78 to 0.94) | 0.001 | 0.7 (0.64 to 0.78) | <0.001 |
| Women | 0.95 (0.86 to 1.05) | 0.3 | 0.87 (0.79 to 0.96) | 0.01 | 0.79 (0.71 to 0.87) | <0.001 | 0.74 (0.66 to 0.83) | <0.001 |
| Race/ethnicity | ||||||||
| White | 0.98 (0.91 to 1.06) | 0.7 | 0.89 (0.82 to 0.96) | 0.003 | 0.81 (0.75 to 0.88) | <0.001 | 0.71 (0.65 to 0.77) | <0.001 |
| Black | 1.08 (0.93 to 1.26) | 0.3 | 0.92 (0.79 to 1.07) | 0.3 | 0.94 (0.81 to 1.1) | 0.5 | 0.77 (0.66 to 0.91) | 0.003 |
| Hispanic | 1.02 (0.76 to 1.37) | 0.9 | 0.82 (0.62 to 1.1) | 0.2 | 0.76 (0.57 to 1.02) | 0.07 | 0.81 (0.59 to 1.11) | 0.2 |
| Other | 0.74 (0.48 to 1.14) | 0.2 | 0.89 (0.56 to 1.4) | 0.6 | 0.76 (0.5 to 1.16) | 0.2 | 0.49 (0.29 to 0.82) | 0.01 |
| Model 2 | ||||||||
| All | 1.01 (0.95 to 1.08) | 0.7 | 0.92 (0.86 to 0.98) | 0.01 | 0.85 (0.79 to 0.91) | <0.001 | 0.73 (0.68 to 0.79) | <0.001 |
| Age, years | ||||||||
| <40 | 0.63 (0.29 to 1.36) | 0.2 | 0.33 (0.14 to 0.75) | 0.01 | 0.73 (0.35 to 1.51) | 0.4 | 0.78 (0.36 to 1.71) | 0.5 |
| 40–64 | 1.05 (0.93 to 1.18) | 0.5 | 0.93 (0.83 to 1.05) | 0.2 | 0.81 (0.71 to 0.92) | 0.001 | 0.74 (0.64 to 0.84) | <0.001 |
| ≥65 | 1 (0.92 to 1.09) | 1 | 0.92 (0.85 to 0.99) | 0.03 | 0.86 (0.79 to 0.94) | <0.001 | 0.73 (0.67 to 0.8) | <0.001 |
| Sex | ||||||||
| Men | 1.04 (0.95 to 1.14) | 0.4 | 0.93 (0.85 to 1.01) | 0.09 | 0.86 (0.79 to 0.94) | 0.001 | 0.7 (0.63 to 0.78) | <0.001 |
| Women | 0.98 (0.89 to 1.08) | 0.7 | 0.9 (0.82 to 1) | 0.05 | 0.82 (0.74 to 0.92) | <0.001 | 0.78 (0.7 to 0.88) | <0.001 |
| Race/ethnicity | ||||||||
| White | 0.99 (0.92 to 1.08) | 0.9 | 0.91 (0.84 to 0.98) | 0.02 | 0.82 (0.76 to 0.89) | <0.001 | 0.71 (0.65 to 0.78) | <0.001 |
| Black | 1.11 (0.95 to 1.29) | 0.2 | 0.99 (0.85 to 1.15) | 0.9 | 0.96 (0.82 to 1.12) | 0.6 | 0.8 (0.68 to 0.95) | 0.01 |
| Hispanic | 1.05 (0.78 to 1.41) | 0.8 | 0.8 (0.6 to 1.06) | 0.1 | 0.78 (0.58 to 1.05) | 0.1 | 0.81 (0.59 to 1.11) | 0.2 |
| Other | 0.81 (0.53 to 1.24) | 0.3 | 0.84 (0.53 to 1.33) | 0.5 | 0.85 (0.56 to 1.3) | 0.5 | 0.54 (0.32 to 0.92) | 0.02 |
| Model 3 | ||||||||
| All | 1.02 (0.95 to 1.09) | 0.5 | 0.93 (0.87 to 0.99) | 0.02 | 0.86 (0.8 to 0.92) | <0.001 | 0.74 (0.68 to 0.79) | <0.001 |
| Age, years | ||||||||
| <40 | 0.53 (0.23 to 1.24) | 0.1 | 0.31 (0.13 to 0.73) | 0.01 | 0.54 (0.25 to 1.17) | 0.12 | 0.53 (0.22 to 1.31) | 0.2 |
| 40–64 | 1.07 (0.94 to 1.2) | 0.3 | 0.94 (0.83 to 1.06) | 0.3 | 0.82 (0.72 to 0.93) | 0.003 | 0.73 (0.63 to 0.83) | <0.001 |
| ≥65 | 1.01 (0.93 to 1.09) | 0.8 | 0.93 (0.86 to 1.01) | 0.07 | 0.88 (0.81 to 0.95) | 0.002 | 0.74 (0.68 to 0.81) | <0.001 |
| Sex | ||||||||
| Men | 1.05 (0.96 to 1.15) | 0.3 | 0.94 (0.86 to 1.03) | 0.2 | 0.88 (0.8 to 0.97) | 0.01 | 0.71 (0.64 to 0.78) | <0.001 |
| Women | 0.99 (0.89 to 1.09) | 0.8 | 0.91 (0.83 to 1.01) | 0.07 | 0.83 (0.75 to 0.92) | 0.001 | 0.79 (0.7 to 0.88) | <0.001 |
| Race/ethnicity | ||||||||
| White | 1 (0.93 to 1.08) | 1 | 0.92 (0.85 to 0.99) | 0.03 | 0.84 (0.77 to 0.91) | <0.001 | 0.72 (0.66 to 0.79) | <0.001 |
| Black | 1.11 (0.96 to 1.29) | 0.2 | 1.01 (0.87 to 1.18) | 0.9 | 1 (0.86 to 1.17) | 1 | 0.81 (0.68 to 0.95) | 0.01 |
| Hispanic | 1.02 (0.76 to 1.39) | 0.9 | 0.77 (0.58 to 1.04) | 0.09 | 0.73 (0.54 to 0.99) | 0.04 | 0.78 (0.56 to 1.07) | 0.1 |
| Other | 0.8 (0.51 to 1.25) | 0.3 | 0.85 (0.53 to 1.36) | 0.5 | 0.8 (0.51 to 1.25) | 0.3 | 0.55 (0.32 to 0.93) | 0.03 |
RRT inception in 2001–2002 is the reference category throughout. Model 1, unadjusted; model 2, adjusted for age, sex, race, and ethnicity; model 3, adjusted for age, sex, race, ethnicity, ischemic heart disease, diabetes, mode of RRT, eGFR, body mass index, serum albumin, and hemoglobin.
Table 4 shows factors associated with mortality, other than year of RRT initiation, for patients with ESRD due to multiple myeloma. Factors associated with mortality (model 1) included: age 40–64 years, age ≥65 years, white race, non-Hispanic ethnicity, ischemic heart disease, diabetes, hemodialysis as mode of RRT, access other than fistula for RRT, shorter duration of nephrologist care, body mass index <30 kg/m2, hemoglobin <9.0 g/dL, and serum albumin <3.5 g/dL. Associations were largely similar after adjustment for baseline demography (model 2) and after full adjustment (model 3). The corresponding overall hazard ratio for death adjusted for baseline demography (AHR) in patients with ESRD due to multiple myeloma versus those with ESRD due to all other causes was 2.05 (95% CI, 1.99 to 2.11; P<0.001). Hazard ratios for death were highest in the first year following RRT initiation (AHR, 2.6; 95% CI, 2.53 to 2.75; P<0.001), and decreased in year 3 (AHR, 1.59; 95% CI, 1.45 to 1.73; P<0.001). Additional characteristics are shown in Supplemental Table 1.
Table 4.
Hazards ratios for death, for patients with multiple myeloma (n=12,702)
| Model 1 | Model 2 | Model 3 | |||||
|---|---|---|---|---|---|---|---|
| Variable | Reference | Hazards Ratio (95% CI) | P value | Hazards Ratio (95% CI) | P value | Hazards Ratio (95% CI) | P value |
| RRT 2003–2004 | 2001–2002 | 1 (0.95 to 1.06)b | 0.99 | 1.02 (0.96 to 1.07)b | 0.59 | 1.02 (0.95 to 1.09)b | 0.55 |
| RRT 2005–2006 | 2001–2002 | 0.9 (0.85 to 0.95) | <0.001 | 0.92 (0.87 to 0.97)c | 0.01 | 0.92 (0.86 to 0.99)d | 0.02 |
| RRT 2007–2008 | 2001–2002 | 0.85 (0.8 to 0.9) | <0.001 | 0.86 (0.81 to 0.91) | <0.001 | 0.86 (0.8 to 0.92) | <0.001 |
| RRT 2009–2010 | 2001–2002 | 0.75 (0.71 to 0.81) | <0.001 | 0.77 (0.72 to 0.82) | <0.001 | 0.76 (0.7 to 0.82) | <0.001 |
| Age <40 years | Age 40–64 years | 0.51 (0.41 to 0.62) | <0.001 | 0.51 (0.41 to 0.63) | <0.001 | 0.55 (0.43 to 0.7) | <0.001 |
| Age ≥65 years | Age 40–64 years | 1.59 (1.52 to 1.65) | <0.001 | 1.58 (1.51 to 1.64) | <0.001 | 1.57 (1.49 to 1.65) | <0.001 |
| Female sex | Male | 0.98 (0.95 to 1.02)b | 0.42 | 0.98 (0.95 to 1.02)b | 0.38 | 1 (0.96 to 1.05)b | 0.83 |
| Black race | White | 0.93 (0.88 to 0.97)c | 0.001 | 0.96 (0.91 to 1)b | 0.07 | 0.91 (0.86 to 0.97)c | 0.002 |
| Other race | White | 0.79 (0.7 to 0.89) | 0.001 | 0.8 (0.71 to 0.91) | <0.001 | 0.73 (0.64 to 0.84) | <0.001 |
| Hispanic ethnicity | Non-Hispanic | 0.87 (0.8 to 0.94) | 0.001 | 0.91 (0.84 to 0.98)d | 0.01 | 0.96 (0.87 to 1.06)b | 0.40 |
| Ischemic heart disease | Absent | 1.22 (1.15 to 1.28) | <0.001 | 1.09 (1.03 to 1.16)c | 0.002 | 1.06 (1 to 1.13)b | 0.06 |
| Diabetes | Absent | 1.12 (1.06 to 1.17) | <0.001 | 1.1 (1.04 to 1.15) | <0.001 | 1.1 (1.03 to 1.16)c | 0.003 |
| Peritoneal dialysis | Hemodialysis | 0.73 (0.65 to 0.81) | <0.001 | 0.72 (0.64 to 0.81) | <0.001 | 0.78 (0.68 to 0.9) | <0.001 |
| Grafta | Fistula | 1.48 (1.12 to 1.95)c | 0.01 | 1.47 (1.12 to 1.94)c | 0.01 | 1.4 (1.02 to 1.93)d | 0.04 |
| Cathetera | Fistula | 1.76 (1.49 to 2.08) | <0.001 | 1.88 (1.6 to 2.22) | <0.001 | 1.94 (1.59 to 2.36) | <0.001 |
| Nephrologist care ≤12 months | ≥12 | 1.22 (1.11 to 1.34) | <0.001 | 1.3 (1.18 to 1.43) | <0.001 | 1.25 (1.12 to 1.39) | <0.001 |
| eGFR >15 mL/min per 1.73 m2 | ≤15 | 1.03 (0.95 to 1.12)b | 0.43 | 1.04 (0.96 to 1.13)b | 0.33 | 1.1 (1 to 1.22)b | 0.05 |
| BMI ≥30 kg/m2 | <30 | 0.87 (0.83 to 0.92) | <0.001 | 0.93 (0.88 to 0.97)c | 0.002 | 0.92 (0.87 to 0.97)c | 0.003 |
| Albumin <3.5 g/dL | ≥3.5 | 1.37 (1.31 to 1.44) | <0.001 | 1.34 (1.28 to 1.41) | <0.001 | 1.32 (1.25 to 1.39) | <0.001 |
| Hemoglobin ≥9 g/dL | <9.0 | 0.9 (0.86 to 0.94) | <0.001 | 0.86 (0.83 to 0.9) | <0.001 | 0.87 (0.83 to 0.92) | <0.001 |
A total of 11,010 patients (86.6%) died over a mean observation period of 1.6 years. Model 1, unadjusted; model 2, adjusted for age, sex, race, and ethnicity; model 3, adjusted for age, sex, race and ethnicity, ischemic heart disease, diabetes, mode of RRT, eGFR, BMI, serum albumin, and hemoglobin. BMI, body mass index.
These analyses were confined to 59.1% of the study population with the 2005 version of the Medical Evidence Report.
P≥0.05.
0.001≤P<0.01.
0.01≤P<0.05.
Discussion
We found that AIRs of ESRD from multiple myeloma declined by nearly 20% between 2001–2002 and 2009–2010, a trend that was largely independent of major demographic characteristics. Mortality rates with multiple myeloma were much higher than with other causes of ESRD, especially in the first year of RRT. Nevertheless, it was encouraging to find that the likelihood of death declined by 28% from 2001–2002 to 2009–2010, and that this trend appeared to be broad demographically, and independent of covariate adjustment strategies.
Given the management changes that have occurred in the past decade, it is surprising that few epidemiologic studies have addressed population-level trends of ESRD due to multiple myeloma. One notable exception was a European study of 13 national registries spanning 1986–2005, treating this era as four separate 5-year intervals.1 Findings differed substantially from those in the current study, as incidence rates rose monotonically and survival on RRT did not improve from 1986–1990 to 2001–2005. A study in the United States from 2001 reported outcomes for 3298 patients with multiple myeloma or light-chain deposition disease, who initiated RRT between 1992 and 1997.13 As in our study, patients with multiple myeloma were disproportionately older, male, and white, and proportions of comorbid conditions were more similar to proportions in the general population than to the recognized burden in prevalent ESRD patients.14 The mortality rate in that study was much higher in patients with than without multiple myeloma; however, temporal trends, incidence ratios, and mortality on RRT were not reported.
The introduction and use of novel agents, including thalidomide, bortezomib, lenalidomide, and carfilzomib, have led to a more targeted approach to therapy and to a trend toward use at earlier disease stages. Widespread integration of these agents into contemporary treatment regimens has demonstrated improvement in both progression-free survival and overall survival.15–20 Thus, it is tempting to speculate that the salutary trends in the management and outlook of multiple myeloma include effects on kidney disease; however, true cause-effect relationships cannot be determined in our study due to its observational nature.
The population-level clinical epidemiology of multiple myeloma may be worth considering.15,21–23 In aggregate, it appears that while the incidence of multiple myeloma is rising, mortality rates are dropping. Because our study used aggregate population estimates, the issue of competing risks between non-renal death and ESRD could not be addressed. If the longer survival of patients with multiple myeloma were through non-renal effects, one might expect a rising incidence of ESRD from multiple myeloma.
Interestingly, we demonstrate a more than two-fold higher incidence of ESRD due to multiple myeloma in black versus white patients (Table 1; incidence ratio 2.15), but a lower hazard of death compared with white patients in both unadjusted and adjusted models (Table 4). These results mirror recent findings from a Surveillance, Epidemiology, and End Results Program study, in which survival rates in black patients with multiple myeloma were significantly higher than in white patients.24 This survival benefit is likely not entirely explained by improved dialysis survival among black versus white patients, suggesting disease heterogeneity by race, as African Americans are less likely to undergo autologous stem cell transplant or to receive chemotherapy than other races.25–27 As secular trends in survival demonstrate a more pronounced improvement in white than in black patients with multiple myeloma, genetic factors, variable treatment response, or perhaps an indolent disease subtype may be among possible reasons that differences exist.28 Recent studies support this concept, as cytogenetic differences in black patients with multiple myeloma suggest a higher prevalence of the trisomic form with better response to treatment; however, further study is needed.28,29
Although mortality trends for the dialysis patients in our study were similar to those for the general population, the rapid improvement in survival over a 10-year period appears noteworthy. Recent Surveillance, Epidemiology, and End Results Program data demonstrate overall improvement in 5-year survival of 29.6% in 1990 to 44.9% in 2010.30 Commensurate with these findings, our data demonstrate both a decrease in the demography-adjusted incidence of ESRD due to multiple myeloma, and in mortality rates in the ESRD subset.
Our study has several limitations, including a retrospective registry-based design and a lack of precise information on renal and bone marrow pathology, markers of disease severity, and medications before and after RRT initiation. Moreover, as our data include all patients with multiple myeloma as cause of ESRD, detailed information regarding outcome associations in patients with newly diagnosed versus relapsed or refractory disease cannot be determined. In addition, we lack information on treatment histories and current therapies. Given the cross-sectional nature of the data, we were unable to ascertain a trajectory of decline leading to initiation of RRT, as the eGFR values were at the time of RRT initiation. In addition, interpretation should be cautious regarding metrics of ESRD care, such as vascular access other than catheter at RRT initiation and duration of nephrology care before RRT initiation, as need for RRT may be the myeloma-defining event. While a prospective longitudinal design with follow-up starting at first diagnosis of multiple myeloma, and regular, scheduled assessments of renal function would be desirable to determine whether the rates of progression to ESRD have truly changed for the better, such a study would be difficult to eventuate. As need for RRT was used as a surrogate for ESRD in this study, the proportion of patients with true ESRD who elected not to receive RRT or withdrew from RRT after initiation is unknown. Our findings also do not reflect patients with AKI requiring RRT, with subsequent recovery, or patients who did not survive the requisite 90 days after the date of RRT initiation for Medicare to defray treatment costs. Howell et al. recently demonstrated that referral to palliative care is significantly higher among patients with multiple myeloma than among patients with other hematologic malignancies (odds ratio, 1.96; 95% CI, 1.15 to 3.35).31 Although relatively small in size and limited to the United Kingdom, this study illustrates contemporary approaches to disease and palliative measures in this patient population. Finally, while it is appealing to posit that therapeutic advances account for the findings of our study, studies with experimental designs with ESRD as primary outcome would be required for confirmation.
In spite of its limitations, we believe that this study provides some useful information. Though research efforts to develop alternative efficacious treatments with fewer side effects are clearly needed, it is encouraging that the risk of ESRD caused by multiple myeloma which then requires RRT appears to be declining, and survival lengthening. While developing mechanism-based targeted treatments are of fundamental importance, findings such as associations between ethnicity, lack of pre-RRT care, temporary dialysis access, and mortality suggest that configuration of nephrology care could also be important in patients with multiple myeloma.
Concise Methods
Objectives
Regarding ESRD due to multiple myeloma necessitating RRT in the United States, this study had two major objectives, namely to evaluate temporal trends for the following between 2001 and 2010: (1) AIRs, relative to rates in 2001–2002; (2) Mortality hazard ratios from initiation of RRT, relative to hazard ratios in 2001–2002.
Subjects
In this retrospective study, we used United States Renal Data System (USRDS) standard analytical files to study American patients who initiated maintenance RRT between 2001 and 2010 (n=1,069,343). Baseline characteristics at initiation of RRT were determined from the Centers for Medicare & Medicaid Medical Evidence Report (form CMS-2728). By federal requirement, this form must be submitted for all new patients starting RRT in the United States, and resultant data are housed in the USRDS Medevid95 and Medevid05 files. The form for the Medical Evidence Report has changed twice in the past two decades, in 1995 and 2005. Unlike previous iterations, the 2005 form includes information about duration of nephrologist care before RRT initiation and vascular access at hemodialysis initiation. On both versions of the form, one of 82 causes is entered as the primary cause of ESRD; options are identical on the 1995 and 2005 versions. For this study, cases of ESRD due to multiple myeloma were those with the primary cause of ESRD listed as “Multiple myeloma” or “Other immunoproliferative neoplasms (including light-chain nephropathy)” on the Medical Evidence Report. Dates of death and cause of death were obtained from the USRDS Patients and Death files.
Statistical Analyses
Data from the United States census were used for population denominators for the years examined, with age in 5-year increments and race/ethnicity classified as non-Hispanic white, non-Hispanic black, Hispanic, and other. Poisson regression was used to calculate population-based incidence ratios of ESRD from multiple myeloma. Chi-squared analysis was used for unadjusted comparisons of patients with and without ESRD due to multiple myeloma, and logistic regression was used for adjusted comparisons. For comparisons of death rates of patients with and without multiple myeloma, patients were matched according to year of dialysis initiation, age (in 1-year intervals), sex, race, and Hispanic ethnicity. Poisson regression was used to compute incidence rates and proportional hazards regression to compute adjusted hazards ratios for death after dialysis initiation, with follow-up ending on June 30, 2012. SAS software, version 9.1.3 (SAS Institute, Cary, NC) was used for data analysis.
Disclosures
None.
Supplementary Material
Acknowledgments
The authors thank Chronic Disease Research Group colleagues Beth Forrest for regulatory assistance, Delaney Berrini for manuscript preparation, and Nan Booth for manuscript editing.
This study was performed under contract no. HHSN267200715002C (National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland).
Footnotes
Published online ahead of print. Publication date available at www.jasn.org.
This article contains supplemental material online at http://jasn.asnjournals.org/lookup/suppl/doi:10.1681/ASN.2014090876/-/DCSupplemental.
References
- 1.Tsakiris DJ, Stel VS, Finne P, Fraser E, Heaf J, de Meester J, Schmaldienst S, Dekker F, Verrina E, Jager KJ: Incidence and outcome of patients starting renal replacement therapy for end-stage renal disease due to multiple myeloma or light-chain deposit disease: an ERA-EDTA Registry study. Nephrol Dial Transplant 25: 1200–1206, 2010 [DOI] [PubMed] [Google Scholar]
- 2.Palumbo A, Anderson K: Multiple myeloma. N Engl J Med 364: 1046–1060, 2011 [DOI] [PubMed] [Google Scholar]
- 3.Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, Stoppa AM, Hulin C, Benboubker L, Garderet L, Decaux O, Leyvraz S, Vekemans MC, Voillat L, Michallet M, Pegourie B, Dumontet C, Roussel M, Leleu X, Mathiot C, Payen C, Avet-Loiseau H, Harousseau JL; IFM Investigators : Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med 366: 1782–1791, 2012 [DOI] [PubMed] [Google Scholar]
- 4.Rajkumar SV, Rosiñol L, Hussein M, Catalano J, Jedrzejczak W, Lucy L, Olesnyckyj M, Yu Z, Knight R, Zeldis JB, Bladé J: Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol 26: 2171–2177, 2008 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS, Avigan DE, Xie W, Ghobrial IM, Schlossman RL, Mazumder A, Munshi NC, Vesole DH, Joyce R, Kaufman JL, Doss D, Warren DL, Lunde LE, Kaster S, Delaney C, Hideshima T, Mitsiades CS, Knight R, Esseltine DL, Anderson KC: Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 116: 679–686, 2010 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, Monconduit M, Hulin C, Caillot D, Bouabdallah R, Voillat L, Sotto JJ, Grosbois B, Bataille R; InterGroupe Francophone du Myélome : Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 349: 2495–2502, 2003 [DOI] [PubMed] [Google Scholar]
- 7.Fermand JP, Katsahian S, Divine M, Leblond V, Dreyfus F, Macro M, Arnulf B, Royer B, Mariette X, Pertuiset E, Belanger C, Janvier M, Chevret S, Brouet JC, Ravaud P; Group Myelome-Autogreffe : High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol 23: 9227–9233, 2005 [DOI] [PubMed] [Google Scholar]
- 8.Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, Abonour R, Siegel DS, Katz M, Greipp PR; Eastern Cooperative Oncology Group : Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol 11: 29–37, 2010 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Mikhael JR, Dingli D, Roy V, Reeder CB, Buadi FK, Hayman SR, Dispenzieri A, Fonseca R, Sher T, Kyle RA, Lin Y, Russell SJ, Kumar S, Bergsagel PL, Zeldenrust SR, Leung N, Drake MT, Kapoor P, Ansell SM, Witzig TE, Lust JA, Dalton RJ, Gertz MA, Stewart AK, Rajkumar SV, Chanan-Khan A, Lacy MQ; Mayo Clinic : Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013. Mayo Clin Proc 88: 360–376, 2013 [DOI] [PubMed] [Google Scholar]
- 10.Chng WJ, Dispenzieri A, Chim CS, Fonseca R, Goldschmidt H, Lentzsch S, Munshi N, Palumbo A, Miguel JS, Sonneveld P, Cavo M, Usmani S, Durie BG, Avet-Loiseau H; International Myeloma Working Group : IMWG consensus on risk stratification in multiple myeloma. Leukemia 28: 269–277, 2014 [DOI] [PubMed] [Google Scholar]
- 11.Palumbo A, Bringhen S, Larocca A, Rossi D, Di Raimondo F, Magarotto V, Patriarca F, Levi A, Benevolo G, Vincelli ID, Grasso M, Franceschini L, Gottardi D, Zambello R, Montefusco V, Falcone AP, Omedé P, Marasca R, Morabito F, Mina R, Guglielmelli T, Nozzoli C, Passera R, Gaidano G, Offidani M, Ria R, Petrucci MT, Musto P, Boccadoro M, Cavo M: Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: updated follow-up and improved survival. J Clin Oncol 32: 634–640, 2014 [DOI] [PubMed] [Google Scholar]
- 12.Korbet SM, Schwartz MM: Multiple myeloma. J Am Soc Nephrol 17: 2533–2545, 2006 [DOI] [PubMed] [Google Scholar]
- 13.Abbott KC, Agodoa LY: Multiple myeloma and light chain-associated nephropathy at end-stage renal disease in the United States: patient characteristics and survival. Clin Nephrol 56: 207–210, 2001 [PubMed] [Google Scholar]
- 14.Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Després JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee : Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation 131: e29–e322, 2015 [DOI] [PubMed] [Google Scholar]
- 15.Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Dingli D, Russell SJ, Lust JA, Greipp PR, Kyle RA, Gertz MA: Improved survival in multiple myeloma and the impact of novel therapies. Blood 111: 2516–2520, 2008 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, Zeddis J, Barlogie B: Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 341: 1565–1571, 1999 [DOI] [PubMed] [Google Scholar]
- 17.Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V, Cangialosi C, Grasso M, Rossini F, Galli M, Catalano L, Zamagni E, Petrucci MT, De Stefano V, Ceccarelli M, Ambrosini MT, Avonto I, Falco P, Ciccone G, Liberati AM, Musto P, Boccadoro M; Italian Multiple Myeloma Network, GIMEMA : Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet 367: 825–831, 2006 [DOI] [PubMed] [Google Scholar]
- 18.Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, Rajkumar SV, Srkalovic G, Alsina M, Alexanian R, Siegel D, Orlowski RZ, Kuter D, Limentani SA, Lee S, Hideshima T, Esseltine DL, Kauffman M, Adams J, Schenkein DP, Anderson KC: A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 348: 2609–2617, 2003 [DOI] [PubMed] [Google Scholar]
- 19.Rajkumar SV, Hayman SR, Lacy MQ, Dispenzieri A, Geyer SM, Kabat B, Zeldenrust SR, Kumar S, Greipp PR, Fonseca R, Lust JA, Russell SJ, Kyle RA, Witzig TE, Gertz MA: Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 106: 4050–4053, 2005 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Bringhen S, Petrucci MT, Larocca A, Conticello C, Rossi D, Magarotto V, Musto P, Boccadifuoco L, Offidani M, Omedé P, Gentilini F, Ciccone G, Benevolo G, Genuardi M, Montefusco V, Oliva S, Caravita T, Tacchetti P, Boccadoro M, Sonneveld P, Palumbo A: Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study. Blood 124: 63–69, 2014 [DOI] [PubMed] [Google Scholar]
- 21.Kristinsson SY, Anderson WF, Landgren O: Improved long-term survival in multiple myeloma up to the age of 80 years. Leukemia 28: 1346–1348, 2014 [DOI] [PubMed] [Google Scholar]
- 22.Pozzi S, Marcheselli L, Bari A, Liardo EV, Marcheselli R, Luminari S, Quaresima M, Cirilli C, Ferri P, Federico M, Sacchi S: Survival of multiple myeloma patients in the era of novel therapies confirms the improvement in patients younger than 75 years: a population-based analysis. Br J Haematol 163: 40–46, 2013 [DOI] [PubMed] [Google Scholar]
- 23.Turesson I, Velez R, Kristinsson SY, Landgren O: Patterns of improved survival in patients with multiple myeloma in the twenty-first century: a population-based study. J Clin Oncol 28: 830–834, 2010 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Waxman AJ, Mink PJ, Devesa SS, Anderson WF, Weiss BM, Kristinsson SY, McGlynn KA, Landgren O: Racial disparities in incidence and outcome in multiple myeloma: a population-based study. Blood 116: 5501–5506, 2010 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Rhee CM, Lertdumrongluk P, Streja E, Park J, Moradi H, Lau WL, Norris KC, Nissenson AR, Amin AN, Kovesdy CP, Kalantar-Zadeh K: Impact of age, race and ethnicity on dialysis patient survival and kidney transplantation disparities. Am J Nephrol 39: 183–194, 2014 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.StatBite : StatBite: Multiple myeloma and African Americans: higher incidence but fewer autologous stem cell transplants. J Natl Cancer Inst 101: 1610, 2009 [DOI] [PubMed] [Google Scholar]
- 27.Rohatgi N, Du XL, Coker AL, Moye LA, Wang M, Fang S: Chemotherapy and survival for patients with multiple myeloma: findings from a large nationwide and population-based cohort. Am J Clin Oncol 30: 540–548, 2007 [DOI] [PubMed] [Google Scholar]
- 28.Greenberg AJ, Philip S, Paner A, Velinova S, Badros A, Catchatourian R, Ketterling R, Kyle RA, Kumar S, Vachon CM, Rajkumar SV: Racial differences in primary cytogenetic abnormalities in multiple myeloma: a multi-center study. Blood Cancer J 5: e279, 2015 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Kumar S, Fonseca R, Ketterling RP, Dispenzieri A, Lacy MQ, Gertz MA, Hayman SR, Buadi FK, Dingli D, Knudson RA, Greenberg A, Russell SJ, Zeldenrust SR, Lust JA, Kyle RA, Bergsagel L, Rajkumar SV: Trisomies in multiple myeloma: impact on survival in patients with high-risk cytogenetics. Blood 119: 2100–2105, 2012 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.National Cancer Institute: Surveillance, Epidemiology, and End Results (SEER) Program, 2014. Available at: http://seer.cancer.gov/data/citation.html. Accessed May 7, 2015
- 31.Howell DA, Wang HI, Roman E, Smith AG, Patmore R, Johnson MJ, Garry AC, Howard MR: Variations in specialist palliative care referrals: findings from a population-based patient cohort of acute myeloid leukaemia, diffuse large B-cell lymphoma and myeloma. BMJ Support Palliat Care 0: 1–7, 2014. [DOI] [PMC free article] [PubMed] [Google Scholar]
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