Interaction between age and gender on survival outcomes in extramedullary multiple myeloma over the past two decades

Table 1 Demographic and Clinicopathologic characteristics of United States patients with extramedullary multiple myeloma between 2000 and 2017

Characteristics	n	%
Total	858	100
Gender
Female	311	36.25
Male	547	63.25
Age at diagnosis, yr
0-39	41	4.78
40-59	309	36.01
60-79	438	51.05
80+	70	8.16
Race
Non-Hispanic white	573	66.78
Non-Hispanic black	133	15.50
Hispanic	110	12.82
Other	42	4.90
Extramedullary site
CNS and vertebral column	284	33.10
Bones, subcutaneous tissues, connective tissues, and soft tissues of the trunk	108	12.59
Bones, soft tissues, subcutaneous tissues, and connective tissues of the pelvis and sacrum	97	11.31
Bones, soft tissues, subcutaneous tissues, connective tissues, and lymph nodes of the upper extremities	64	7.46
Bones, soft tissues, subcutaneous tissues, and connective tissues of the lower extremities	45	5.24
Bones, soft tissues, subcutaneous tissues, connective tissues, and lymph nodes of the face and skull	60	6.99
Other bones, NOS	37	4.31
Eyes, mouth, and ENT	101	11.77
Lung, breast, and mediastinum	26	3.03
Gastrointestinal tract	18	2.10
Skin	12	1.40
Kidney, suprarenal glands, and retroperitoneum	6	0.70
Living area
Counties in metropolitan areas of 1 million persons	481	56.06
Counties in metropolitan areas of 250000 to 1 million persons	173	20.16
Counties in metropolitan areas of 250000 persons	76	8.86
Nonmetropolitan counties adjacent to a metropolitan area	77	8.97
Nonmetropolitan counties not adjacent to a metropolitan area	51	5.94
Income per year
< $35000	12	1.40
$35000-44999	74	8.62
$45000-54999	154	17.95
$55000-64999	232	27.04
$65000-74999	183	21.33
$75000+	203	23.66
Marital Status
Married	569	66.32
Single	106	12.35
Divorced/separated	79	9.21
Widowed	62	7.23
Unknown	42	4.90

CNS: Central Nervous System; NOS: Not otherwise specified.

Table 2 Crude analysis of factors associated with all-cause mortality and extramedullary multiple myeloma; related mortality among United States patients between 2000 and 2017

Characteristics	Overall mortality	EMD MM mortality
	Crude proportional-hazard ratio (95% confidence interval)
Gender
Female	1 (reference)	1 (reference)
Male	1.02 (0.826-1.259)	0.804 (0.611-1.056)
Age at diagnosis, yr
0-39	1 (reference)	1 (reference)
40-59	1.683 (0.82-3.452)	2.409 (0.754-7.696)
60-79	3.271 (1.615-6.627)c	4.918 (1.565-15.461)c
80+	6.951 (3.299-14.647)c	10.111 (3.083-33.159)c
Race
Non-Hispanic white	1 (reference)	1 (reference)
Non-Hispanic black	1.339 (1.02-1.759)b	1.446 (1.017-2.055)b
Hispanic	0.991 (0.719-1.365)	0.791 (0.495-1.263)
Other	1.016 (0.63-1.639)	1.209 (0.67-2.179)
Extramedullary site
CNS and vertebral column	1 (reference)	1 (reference)
Bones, subcutaneous tissues, connective tissues, and soft tissues of the trunk	1.53 (1.113-2.102)c	1.187 (0.774-1.82)
Bones, soft tissues, subcutaneous tissues, and connective tissues of the pelvis and sacrum	1.027 (0.716-1.475)	1.15 (0.746-1.772)
Bones, soft tissues, subcutaneous tissues, connective tissues, and lymph nodes of the upper extremities	1.036 (0.682-1.573)	0.718 (0.391-1.32)
Bones, soft tissues, subcutaneous tissues, and connective tissues of the lower extremities	1.668 (1.058-2.63)b	1.466 (0.814-2.642)
Bones, soft tissues, subcutaneous tissues, connective tissues, and lymph nodes of the face and skull	1.135 (0.756-1.702)	0.919 (0.529-1.598)
Other bones, NOS	1.74 (1.043-2.902)b	1.887 (1.044-3.411)b
Eyes, mouth, and ENT	0.929 (0.668-1.293)	0.451 (0.259-0.783)c
Lung, breast, and mediastinum	1.588 (0.895-2.816)	1.278 (0.589-2.773)
Gastrointestinal tract	0.787 (0.367-1.688)	0.55 (0.174-1.745)
Skin	0.241 (0.06-0.974)b	0.195 (0.027-1.403)
Kidney, suprarenal glands, and retroperitoneum	1.861 (0.591-5.86)	0.907 (0.126-6.531)
Living area
Counties in metropolitan areas of 1 million persons	1 (reference)	1 (reference)
Counties in metropolitan areas of 250000 to 1 million persons	1.021 (0.789-1.322)	0.803 (0.556-1.158)
Counties in metropolitan areas of 250000 persons	0.794 (0.538-1.17)	0.8 (0.482-1.327)
Nonmetropolitan counties adjacent to a metropolitan area	1.099 (0.775-1.559)	0.937 (0.578-1.518)
Nonmetropolitan counties not adjacent to a metropolitan area	1.191 (0.798-1.779)	1.105 (0.647-1.888)
Income per year
< $35000	1 (reference)	1 (reference)
$35000-44999	0.457 (0.213-0.984)b	0.412 (0.167-1.014)a
$45000-54999	0.356 (0.17-0.745)c	0.33 (0.139-0.782)b
$55000-64999	0.358 (0.174-0.737)c	0.236 (0.101-0.554)c
$65000-74999	0.328 (0.158-0.681)c	0.292 (0.124-0.685)c
$75000+	0.259 (0.125-0.538)c	0.24 (0.102-0.563)c
Marital status
Married	1 (reference)	1 (reference)
Single	1.305 (0.967-1.763)a	1.515 (1.027-2.236)b
Divorced/separated	1.531 (1.094-2.142)b	1.681 (1.084-2.605)b
Widowed	2.107 (1.511-2.938)c	2.463 (1.612-3.765)c

^aP < 0.1.

^bP < 0.05.

^cP < 0.01.

EMD: Extramedullary disease; MM: Multiple myeloma; CNS: Central Nervous System; NOS: Not otherwise specified.

Table 3 Multivariate cox proportional hazard regression analyses of factors affecting all-cause mortality and extramedullary disease multiple myeloma related mortality among United States patients between 2000 and 2017

Characteristics	Overall mortality	EMD MM mortality
	Adjusted proportional hazard ratio (95% confidence interval)
Gender
Female	1 (reference)	1 (reference)
Male	1.256 (0.989-1.594)a	1.022 (0.748-1.397)
Age at diagnosis, yr
0-39	1 (reference)	1 (reference)
40-59	2.206 (1.047-4.647)b	3.154 (0.957-10.395)a
60-79	4.129 (1.974-8.635)c	5.667 (1.738-18.48)c
80+	9.792 (4.403-21.774)c	13.672 (3.915-47.746)c
Race
Non-Hispanic white	1 (reference)	1 (reference)
Non-Hispanic black	1.315 (0.96-1.802)a	1.34 (0.884-2.03)
Hispanic	1.034 (0.734-1.457)	0.833 (0.506-1.371)
Other	1.25 (0.743-2.104)	1.741 (0.916-3.308)a
Extramedullary site
CNS and vertebral column	1 (reference)	1 (reference)
Bones, subcutaneous tissues, connective tissues, and soft tissues of the trunk	1.401 (0.996-1.972)a	1.046 (0.664-1.649)
Bones, soft tissues, subcutaneous tissues, and connective tissues of the pelvis and sacrum	0.98 (0.671-1.432)	1.091 (0.689-1.729)
Bones, soft tissues, subcutaneous tissues, connective tissues, and lymph nodes of the upper extremities	1.024 (0.661-1.586)	0.672 (0.353-1.279)
Bones, soft tissues, subcutaneous tissues, and connective tissues of the lower extremities	1.488 (0.909-2.436)	1.382 (0.733-2.605)
Bones, soft tissues, subcutaneous tissues, connective tissues, and lymph nodes of the face and skull	0.99 (0.641-1.53)	0.76 (0.414-1.394)
Other bones, NOS	1.195 (0.694-2.058)	1.199 (0.629-2.284)
Eyes, mouth, and ENT	0.902 (0.631-1.29)	0.425 (0.235-0.768)c
Lung, breast, and mediastinum	1.187 (0.628-2.246)	0.959 (0.392-2.346)
Gastrointestinal tract	0.677 (0.303-1.512)	0.383 (0.114-1.283)
Skin	0.327 (0.08-1.34)	0.325 (0.044-2.394)
Kidney, suprarenal glands, and retroperitoneum	3.055 (0.881-10.601)a	0.865 (0.108-6.901)
Living area
Counties in metropolitan areas of 1 million persons	1 (reference)	1 (reference)
Counties in metropolitan areas of 250000 to 1 million persons	0.957 (0.715-1.282)	0.778 (0.512-1.181)
Counties in metropolitan areas of 250000 persons	0.819 (0.523-1.282)	0.85 (0.47-1.539)
Nonmetropolitan counties adjacent to a metropolitan area	0.997 (0.653-1.522)	0.836 (0.461-1.516)
Nonmetropolitan counties not adjacent to a metropolitan area	0.877 (0.533-1.442)	0.757 (0.379-1.512)
Income per year
< $35000	1 (reference)	1 (reference)
$35000-44999	0.48 (0.21-1.095)a	0.381 (0.14-1.036)a
$45000-54999	0.452 (0.196-1.04)a	0.375 (0.135-1.044)a
$55000-64,999	0.446 (0.192-1.036)a	0.275 (0.096-0.788)b
$65000-74999	0.413 (0.173-0.983)b	0.381 (0.129-1.121)a
$75000+	0.324 (0.134-0.783)b	0.29 (0.095-0.878)b
Marital status
Married	1 (reference)	1 (reference)
Single	1.5 (1.079-2.086)b	1.668 (1.089-2.556)b
Divorced/separated	1.49 (1.037-2.139)b	1.463 (0.908-2.355)
Widowed	1.609 (1.101-2.35)b	2.085 (1.275-3.409)c

^aP < 0.1.

^bP < 0.05.

^cP < 0.01.

EMD: Extramedullary disease; MM: Multiple myeloma; CNS: Central Nervous System; NOS: Not otherwise specified.

Table 4 Joint test analysis of the predictors of extramedullary multiple myeloma and overall mortality among United States extramedullary multiple myeloma patients, 2000-2017

Variables	MM mortality			Overall mortality
	DF	χ2	P value	χ2	P value
Race/ethnicity	3	5.7436	0.1248	3.2403	0.3560
Age at diagnosis	3	21.2193	< 0.0001	49.2869	< 0.0001
Gender	1	0.5044	0.4776	0.5168	0.4722
Extramedullary Site	11	16.6070	0.1200	15.6578	0.1543
Living area	4	2.1023	0.7169	0.8175	0.9361
Income	5	7.3539	0.1956	7.4157	0.1915
Marital status	3	10.8183	0.0128	11.7967	0.0081
chemotherapy	1	2.3104	0.1285	1.4536	0.2280
Year of diagnosis	17	25.3142	0.0879	16.1848	0.5108
Interaction between age and gender	3	2.1285	0.5462	1.0296	0.7941

DF: Degree of freedom; MM: Multiple myeloma.