Incidence and mortality of multiple myeloma in China, 2006–2016: an analysis of the Global Burden of Disease Study 2016

Multiple myeloma (MM) is the second most frequent hematological disease worldwide [1]. In 2016, the incident cases of MM in the most populous countries were 139,000 with the rank of 26 among all cancers, and death number was 98,000 with the rank of 22 among all cancers [2]. According to the statistics of GLOBOCAN 2018, MM accounted for 0.9% of all new cancer cases and 1.1% of all cancer deaths worldwide in 2018 [3]. A recent study estimated that there were 52,000 deaths associated with lymphoma and myeloma and the age-standardized mortality rate was 3.74 per 100,000 population in China in 2017.While the age-standardized mortality rate for lymphoma and myeloma worldwide was 2.60 per 100,000 population. Moreover, the mortality rates of lymphoma and myeloma increased annually by 4.5% from 2004 to 2016 in China [4].

Until now, accurate epidemiologic study of MM based on national and province level has not been conducted in China. In this analysis, we sought to determine the incidence and mortality of multiple myeloma in China in 2016 and analyze temporal trends from 2006 to 2016.

The present study is the most comprehensive evaluation of the large and ever-growing burden of multiple myeloma in China. Due to the standardized methods for estimates of multiple myeloma metrics used in the GBD study, it is possible to compare incidence and mortality at province level in China. Based on the disparities in disease burden, different strategies for disease prevention and control should be employed when health policy is developed in the future.

The patterns of burden of MM varied by age and sex. Unlike most other cancers in China, MM was rare between 0–14 years old. Both incidence and mortality rate were increased with age in most of the age groups, which was consistent with previous study published by our group [4]. Notably, male predominance of incidence and mortality was seen in all age groups. According to the GBD study, both the age-standardized incidence and mortality rate in China were lower than global (ASIR was 1.93 per 100,000 population with 95% UI 1.87–2.19, ASMR was 1.37 per 100,000 population with 95% UI 1.26–1.52) and our neighbor Japan (ASIR was 2.18 per 100,000 population with 95% UI 1.91–2.78, ASMR was 1.30 per 100,000 population with 95% UI 1.17–1.58) [5, 7]. Geographical differences across provinces had an important role in the epidemiological characteristics of MM in China. Overall, higher incidence and mortality rates were seen in the clustered developed provinces, with 2–3-fold gap between those developed and less-developed provinces. In addition, the incidence level in the developed provinces was more close to those developed countries in Asia, like Japan. The low incidence and mortality rates in less-developed provinces may be associated with the poor medical accessibility. The heterogeneous pattern of epidemiological characteristics of MM across provinces highlighted the need to improve the access to health services leading to more precise diagnosis and early treatment, especially in those less-developed provinces.

Improving diagnosis and treatment techniques had a positive effect on the mortality of MM. The result of EUROCARE-5 [8] reflected the encouraging trend of MM and plasmacytoma with survival increase from 29.8% in 1997–1999 to 39.6% in 2006–2008. High-dose chemotherapy followed by autologous hematopoietic cell transplantation changed dramatically the perspective for young patients, while novel agents such as bortezomib, thalidomide, and lenalidomide prolonged the survival for both young and elderly patients [1]. Real-world study from the Swedish Myeloma Registry showed that the 5-year relative survival increased from 47.3% in the period of 2008–2010 to 51.3% in the period of 2011–2015 with the increased use of novel agents [9]. Another study from the Swedish Cancer Register also showed that the 10-year mortality in patients younger than 60 years in 1994–2003 reduced 29% compared with that in 1987–1993 [10]. A study from the Asian Myeloma Network, involving 3405 symptomatic MM patients, demonstrated that the median overall survival was 47 months (95% CI 44.0–50.0) and better survival was observed in those treated with stem cell transplantation or new drugs [11]. In a multicenter study [12] including 940 newly diagnosed MM patients from China, the median overall survival (OS) was 54 months with more survival benefit in IgG patients receiving bortezomib. Notably, the Food and Drug Administration of China approved bortezomib in 2005 and lenalidomide in 2013 for the treatment of MM. Until then, the Chinese patients had a chance of being exposed to novel drugs because they received treatment with many clinical trials in tertiary hospitals [11]. In our study, the mortality of MM increased from 2006 to 2014, but remained stable since 2014, regardless of the continuous increasing incidence. Similarly, a systematic analysis for global burden of MM [13] demonstrated that there was an improvement in age-standardized death rate form from 1990 to 2016 in high-income sociodemographic index regions despite increasing incidence rates, which indicated that patients with MM, especially in developed areas, benefited from treatment advancement. All these findings suggested modern risk-adaptive therapies brought longer survival for MM patients and then led to decrease of mortality of MM. There are marked differences in the epidemiological characteristics of MM between western and eastern countries. Increasing incidence trends were verified for most of the European and American countries, which was attributed to better accessibility to health services and more precise diagnosis of MM [14]. In Great Britain, the MM age-adjusted incidence per100,000 increased from 3.2 in 1975–1979 to 5.4 in 2005–2009. In addition, the data in this study argued strongly against the notion that environmental exposures were responsible for the changes in incidence [15]. In the USA, the incidence rates of MM per 100,000 remained stable over the three decades, with 4.6 in 1981–1990, 4.7 in 1991–2000, and 4.7 in 2001–2010, respectively [16]. In our study, we determined that the burden of MM was increasing in China during the past decade. This upward trend of incidence may be explained partly by some factors such as aging, better access to diagnosis, excess body weight [17], and occupational exposures [18], but much of this trend was largely unexplained and further study focused on etiology of MM should be performed.

The interpretation of our study has several limitations. First, all the general limitations described by the GBD collaboration group [5‐7, 19] apply to the present study. Second, the low incidence and mortality rates of MM both in the national level and in the province levels may bias the estimated results using the standard GBD methodology. Third, population growth and changes of socioeconomic structures should also be taken into account; the spatial-temporal trends of MM burden needs to be interpreted cautiously.

This is the first study to present spatiotemporal variation in MM burden in China nationally. Higher incidence and mortality rates were observed in males and older individuals with geographical differences across provinces. A significant increase in the incidence of MM was notable. The study results will be useful for policy-making with respect to disease prevention and the development of management strategies.