Trends In The Incidence Of Mm
Since 1990, the global incident cases of MM increased 136.10%, and reached 1,556.88×102 (95% uncertainty interval [UI]: (1,365.85×102 to 1,725.77×102)) in 2019. The overall age-standardized incidence rate (ASIR)/100,000 population increased from 1.73 in 1900 to 1.92 in 2019, by an annual average of 136.10% (EAPC = 0.25, 95%CI: 0.15 to 0.35) (Table 1; Fig. 1). Incident cases of MM increased with age, and those aged over 80 years had the largest increasing percentage (229.85%) (Supplementary Table 1; Fig. 2A). Compared to females, males had a higher rising trend in ASIR (EAPC = 0.43, 95%CI: 0.33 to 0.53). Among 21 geographic regions, the incident number ranged from 0.72×102 in Oceania to 389.81×102 in Western Europe in 2019. The highest increasing percentage occurred in Tropical Latin America (284.74%). The ASIR varied from 0.80 in Central Asia to 5.33 in Australasia in 2019. 1990–2019, twenty regions presented upward trends of ASIR, and Eastern Europe had the largest one (EAPC = 1.40, 95%CI: 1.24 to 1.56), except Oceania (EAPC = -0.08, 95%CI: -0.12 to -0.05) (Table 1; Fig. 1, and 2B-C). Among 204 countries/territories, the largest incident cases of MM occurred in San Marino (270.54×102), followed by Nauru and Ethiopia. The ASIRs of MM were heterogeneous across countries, ranging from 0.62 in Kyrgyzstan to 14.95 in Monaco in 2019. During 1990–2019, the percentages of incident cases pronouncedly increased in the United Arab Emirates (985.12%) and Qatar (838.57%), but decreasing ones occurred in Tokelau (-8.78%) and Niue (-0.74%). 158countries undertook increasing trends in the ASIR of MM from 1990 to 2019, and Jamaica and Belarus had the largest ones, in which the respective EAPCs of 4.15 (95%CI: 3.41 to 4.90) and 3.25 (95%CI: 2.99 to 3.51). However, 23 countries presented decreasing trends, particularly the Northern Mariana Islands (EAPC = -1.29, 95%CI: -1.48 to -1.00). (Supplementary Table 2; Figs. 3A-C).
Table 1
The characteristics and changes in the incidence of multiple myeloma in global and regions from 1990 to 2019.
| 1990 | 2019 | 1990–2019 |
Characteristics | Number ×102 (95% UI) | ASR/100,000 (95% UI) | Number ×102 (95% UI) | ASR/100,000 (95% UI) | Percentage (%) | EAPC (95%CI) |
Overall | 659.41 (607.8–740.59) | 1.73 (1.59–1.93) | 1556.88 (1365.85–1725.77) | 1.92 (1.68–2.12) | 136.10 | 0.25 (0.15–0.35) |
Sex | | | | | | |
Male | 334.35 (295.82–387.97) | 1.97 (1.74–2.25) | 845.16 (709.24–949.1) | 2.28 (1.91–2.56) | 152.78 | 0.43 (0.33–0.53) |
Female | 325.05 (293.74–380.2) | 1.55 (1.40–1.81) | 711.71 (603.43–801.4) | 1.62 (1.38–1.83) | 118.95 | 0.02 (-0.09–0.13) |
SDI | | | | | | |
Low | 22.74 (17.82–30.75) | 0.97 (0.77–1.29) | 51.48 (41.01–59.81) | 1.00 (0.80–1.16) | 126.43 | 0.34 (0.27–0.41) |
Low-middle | 48.96 (41.32–67) | 0.82 (0.7–1.11) | 136.54 (118.31–158.09) | 0.99 (0.86–1.15) | 178.91 | 0.67 (0.64–0.70) |
Middle | 86.55 (75.36–108.38) | 0.84 (0.74–1.04) | 252.94 (209.19–286.29) | 1.01 (0.83–1.14) | 192.24 | 0.81 (0.75–0.87) |
High-middle | 160.24 (148.54–181.97) | 1.51 (1.4–1.71) | 373.29 (309.33–418.06) | 1.83 (1.52–2.05) | 132.96 | 0.64 (0.54–0.74) |
High | 340.48 (301.34–361.51) | 3.23 (2.84–3.43) | 722.50 (626.1–825.2) | 3.77 (3.29–4.33) | 112.20 | 0.33 (0.17–0.49) |
Regions | | | | | | |
East Asia | 63.69 (52.43–89.24) | 0.71 (0.59–0.99) | 197.12 (144.45–242.87) | 0.94 (0.69–1.16) | 209.48 | 1.05 (0.99–1.11) |
South Asia | 45.16 (35.36–56.49) | 0.82 (0.64–1.01) | 133.68 (97.87–159.41) | 0.95 (0.69–1.13) | 196.03 | 0.49 (0.45–0.54) |
Southeast Asia | 18.20 (15.43–24.76) | 0.71 (0.6–0.97) | 50.03 (41.74–65.94) | 0.82 (0.68–1.09) | 174.87 | 0.48 (0.43–0.53) |
Central Asia | 2.82 (2.39–3.19) | 0.60 (0.50–0.68) | 6.08 (5.33–6.86) | 0.80 (0.70–0.89) | 115.82 | 1.10 (1.00–1.21) |
High-income Asia Pacific | 35.27 (31.93–38.95) | 1.77 (1.60–1.96) | 91.91 (71.32–108.88) | 1.96 (1.58–2.3) | 160.62 | 0.37 (0.22–0.52) |
Oceania | 0.30 (0.20–0.51) | 1.02 (0.68–1.68) | 0.72 (0.48–1.14) | 1.01 (0.69–1.55) | 135.96 | -0.08 (-0.12–-0.05) |
Australasia | 10.05 (8.71–10.85) | 4.26 (3.68–4.6) | 26.58 (21–33.88) | 5.33 (4.21–6.8) | 164.38 | 0.61 (0.42–0.79) |
Eastern Europe | 31.40 (27.79–35.91) | 1.10 (0.97–1.28) | 53.58 (46.43–60.83) | 1.57 (1.35–1.78) | 70.67 | 1.40 (1.24–1.56) |
Western Europe | 189.83 (174.75–215.70) | 3.26 (3.00–3.67) | 389.81 (317.27–447.10) | 4.24 (3.51–4.90) | 105.34 | 0.68 (0.46–0.90) |
Central Europe | 23.17 (21.95–26.75) | 1.55 (1.47–1.79) | 45.50 (35.99–52.49) | 2.13 (1.69–2.46) | 96.34 | 1.10 (0.93–1.27) |
High-income North America | 152.60 (128.15–158.75) | 4.32 (3.62–4.50) | 303.94 (260.16–368.35) | 4.80 (4.12–5.87) | 99.18 | 0.11 (-0.02–0.25) |
Andean Latin America | 2.99 (2.41–4.19) | 1.48 (1.19–2.06) | 9.55 (7.47–12.14) | 1.71 (1.34–2.18) | 219.37 | 0.74 (0.62–0.85) |
Central Latin America | 9.63 (8.99–10.66) | 1.14 (1.07–1.28) | 39.27 (32.69–46.45) | 1.65 (1.38–1.96) | 307.79 | 1.17 (1.08–1.25) |
Caribbean | 6.59 (5.71–7.82) | 2.55 (2.21–3.02) | 16.86 (14.01–19.93) | 3.25 (2.70–3.84) | 155.63 | 0.94 (0.89–0.99) |
Tropical Latin America | 13.01 (12.29–14.86) | 1.41 (1.33–1.63) | 50.04 (43.5–53.94) | 2.06 (1.78–2.22) | 284.74 | 1.30 (1.14–1.46) |
Southern Latin America | 9.61 (8.42–10.87) | 2.07 (1.82–2.34) | 22.12 (17.28–28.37) | 2.66 (2.08–3.41) | 130.12 | 0.71 (0.57–0.85) |
Eastern Sub- Saharan Africa | 8.48 (6.23–11.15) | 1.16 (0.86–1.49) | 20.34 (14.37–25.01) | 1.28 (0.91–1.56) | 139.81 | 0.38 (0.35–0.4) |
Southern Sub- Saharan Africa | 5.05 (4.04–5.83) | 1.83 (1.45–2.1) | 12.67 (9.05–14.67) | 2.24 (1.60–2.59) | 150.76 | 0.71 (0.52–0.91) |
Western Sub- Saharan Africa | 6.89 (5.58–8.79) | 0.79 (0.64–1.01) | 17.05 (13.4–20.74) | 0.91 (0.72–1.11) | 147.30 | 0.57 (0.52–0.61) |
North Africa and Middle East | 22.04 (17.57–29.33) | 1.29 (1.04–1.7) | 63.73 (49.91–76.41) | 1.49 (1.17–1.77) | 189.23 | 0.52 (0.42–0.63) |
Central Sub- Saharan Africa | 2.61 (1.83–3.52) | 1.16 (0.81–1.54) | 6.30 (3.90–8.64) | 1.20 (0.74–1.64) | 141.27 | 0.12 (0.05–0.18) |
EAPC: estimated annual percentage change; ASR, age-standardized rate; CI, confidence interval; UI: uncertainty interval; SDI: socio-demographic index. |
Trends in death caused by MM
In 2019, the death number of MM was 1134.74×102 (95%UI: 995.27×102 to 1217.35×102) globally, with an increase of 118.80% since 1990. The overall age-standardized death rate (ASDR) was 1.42 in 2019, and it was relatively stable from 1990 to 2019 (Supplementary Table 3; Fig. 1). Death caused by MM increased with age, and those aged over 80 years had the largest increasing percentage (211.82%) (Supplementary Table 1; Supplementary Fig. 1A). Male patients had a higher burden than female patients. Male patients had an increasing trend of ASDR, but female patients had decreasing one (EAPC = -0.28, 95%CI: -0.37 to -0.19) from 1999 to 2019. In terms of geographic regions, the largest number of Death varied from 0.63×102 in Oceania to 259.96×102 in Western Europe in 2019. Meanwhile, the ASDR went up from 0.68 in East Asia to 3.07 in High-income North America. 1990 to 2109, trends in the ASDR of MM increased in most regions, particularly Tropical Latin America (EAPC = 1.07, 95%CI: 0.93 to 1.22). However, three regions had decreasing trends, including High-income North America and High-income Asia Pacific, with the respective EAPCs of -0.31 (95%CI: -0.42 to -0.21) and − 0.31 (95%CI: -0.46 to -0.16) (Supplementary Table 3; Fig. 1, and Supplementary Figs. 1B-C). At the national level, the United States of America, China, and India had the largest death number of MM, which were 179.42×102, 134.21×102, and 90.56×102, respectively. The ASDR varied from 0.55 in Kyrgyzstan to 9.81 in Monaco in 2019. From 1990 to 2019, the percentage of death number changed significantly in the United Arab Emirates (862.59%) and Qatar (662.73%), but declined only in Tokelau (-15.25%) and Niue (-8.55%). 124 countries/territories presented increasing trends from 1990 to 2019, and Jamaica and Belarus had the most pronounced ones, in which the respective EAPCs were 3.96 (95%CI: 3.20 to 4.72) and 2.61 (95%CI: 2.31 to 2.91). On the other hand, 40 countries/territories showed decreasing trends, particularly Jordan (EAPC = -1.61, 95%CI: -1.82 to -1.40) (Supplementary Table 4; Figs. 3D-F).
Trends in DALYs caused by MM
The global number of DALYs caused by MM increased 104.13% since 1990, and reached 24,972.05×102 (95%UI: 21,904.67×102 to 27,226.69×102) in 2019. The trend in the overall ASR of DALYs declined from 1990 to 2019, with the EAPC of -0.16 (95%CI: -0.23 to -0.09). (Supplementary Table 3; Fig. 1). Among the age groups, those aged 60–74 years had the highest death, and those aged over 80 years had the largest increase of 199.99% (Supplementary Table 1; Supplementary Fig. 2A). Compared to male patients, female patients undertook a lower burden, and had a larger decreasing trend of ASR (EAPC= -0.38, 95%CI: -0.46 to -0.30). At the regional level, the number of DALYs varied from 18.28×102 in Oceania to 4,616.32×102 in Western Europe in 2019. The ASR of DALYs ranged from 16.90 in Southeast Asia to 63.18 in High-income North America. 1990–2019, the percentage of DALYs number changed from 49.43% in Eastern Europe to 249.21% in Andean Latin America. Increasing trends in the ASR of DALYs occurred in most regions, particularly Central Asia (EAPC = 1.06, 95%CI: 0.98 to 1.14). However, three regions had decreasing trends, including High-income North America (EAPC = -0.6, 95%CI: -0.71 to -0.49) and High-income Asia Pacific (EAPC = -0.49, 95%CI: -0.61 to -0.36) (Supplementary Table 3; Fig. 1, and Supplementary Figs. 2B-C). Among 204 countries/territories, the United States of America had the largest number of DALYs (3502.37×102), followed by China and India. The ASR of DALYs in 2019 varied from 13.33 in Kyrgyzstan to 199.23 in Monaco. The number of DALYs rose significantly in the United Arab Emirates (934.57%) and Qatar (655.21%) from 1990 to 2019, but decreased in Tokelau (-12.36%) and Niue (-6.42%). Trends in the ASR of DALYs caused by MM increased in 115 countries/territories, particularly Jamaica and Turkmenistan, in which the respective EAPCs were 4.01 (95%CI: 3.29 to 4.74) and 2.99 (95%CI: 2.69 to 3.29). On the other hand, trends declined in 63 countries/territories, and the most pronounced one was observed in Bahrain (EAPC = -1.77, 95%CI: -1.93 to -1.61), followed by Jordan and the Northern Mariana Islands (Supplementary Table 5; Figs. 3G-I).
Trends of the MM burden related to SDI
Among five SDI areas, the high SDI area had the highest burden of MM, with incident cases of 722.50×102, and undertook 481.08×102 death and 9011.83×102 DALYs in 2019. The ASIR of MM ranged from 1.00 in low SDI areas to 3.77 in high one.1990 to 2019, increasing trends of ASIR occurred in all SDI areas, particularly Middle areas (EAPC = 0.81, 95%CI: 0.75 to 0.87) (Table 1; Figs. 1, and 2D). The high SDI area had the largest ASR of death and DALYs, which were 2.4 and 49.30 in 2019, respectively. ASR of death and DALYs increased in most SDI regions from 1990 to 2019, particularly in low-middle and middle SDI areas. However, trends declined in the high SDI area, with respective EAPCs of -0.17 (95%CI: -0.29 to -0.04) and − 0.35 (95%CI: -0.48 to -0.22) (Supplementary Table 3; Fig. 1, and Supplementary Figs. 1, and 2D). Positive associations were demonstrated between ASRs of incidence, death, and DALYs and SDI among regions in 2019 (ρ = 0.66, p < 0.001; ρ = 0.60, p < 0.001; ρ = 0.57, p < 0.001; Figs. 4A-C).
Analysis of the influential factors of EAPC
The ASR in 1990 is considered the disease reservoir at baseline. The EAPCs had a negative association with the corresponding ASRs of death and DALYs in 1990 (ρ = -0.17, p = 0.016; ρ = -0.19, p = 0.008, respectively; Supplementary Fig. 3A-B), but not with that of incidence. The HDI reflected the socioeconomic development status, and the accessibility of health resources in regions and countries. Only the EAPCs of incidence had a positive association with HDI in 2019 (ρ = 0.18, p = 0.011; Supplementary Fig. 4).