Multiple Myeloma in Asia

Multiple myeloma (MM) is one of the most common hematologic malignancies, with 114,252 new cases and 80,119 deaths worldwide annually in 2012, comprising 0.8% and 1% of all cancers, respectively[1]. Its incidence is known to vary by ethnicity, with Asians showing a relatively lower incidence than Caucasians by IARC data as well as US SEER data even within a country. [1] Although the incidence is lower, the actual number of new cases of multiple myeloma in Asia (35,828) was higher than that of North America (31,613) in 2012 because of its huge population.

We do not know exactly why Asian people have lower susceptibility to multiple myeloma. However, there are few reports reporting genetic polymorphism is related to it. [2-5]

Moreover, recent reports have suggested that the incidence of multiple myeloma is increasing in Asian countries, including Korea, Taiwan, and Thailand [6-8]. The reasons of this increase are speculated to be related to rapid industrialization and increased life span, which are common trends among Asian countries. Aging is especially related to the MGUS incidence, from which active MM develops.

Recent studies from several Asian countries showed substantial increase of MGUS with aging. [9-12]. For example, Park et al. [9] reported that, among 1,118 elderly (age ≥ 65 years) members of an urban Korean population, the age- and gender-adjusted MGUS prevalence was 3.3% , which is only slightly lower than the Western data. A subsequent Korean study showed that the natural clinical course of MGUS, including the rate of progression to multiple myeloma in Korea (1%/year), is similar to that in Western countries [13].

There have been reports describing the clinical profiles [14–16] as well as the cytogenetic characteristics [17–19] of MM in Asia, with some studies revealing unique findings in their national cohorts. Also, there have been reports describing unique drug toxicity profiles such as interstitial pneumonitis among Japanese bortezomib users [20,21], as well as lower incidence of thromboembolism among thalidomide users in some Asian countries, even without antithrombotic prophylaxis, strongly suggesting differences in pharmacogenomics [22,23].

Although several studies on the clinical features of multiple myeloma in Asian countries have been published, all of them were nationwide studies that did not include a variety of Asian ethnicities and did not incorporate recent changes in epidemiology and medical practices.

Recognizing the need for Asian multinational studies, the Asian Myeloma Network (AMN) was launched in March 2011 under the auspices of the International Myeloma Foundation (IMF) with the participation of seven countries and regions, which already had national myeloma study groups at the time: China, Hong Kong, Japan, Korea, Singapore, Taiwan, and Thailand.

Our first question was whether multiple myeloma in Asia has characteristics that differ from its presentation in Western countries as non-Hodgkin lymphoma in Asia has shown different subtype distribution. As our first project, we conducted a multinational study to define the clinical characteristics of MM in Asian countries. [24]

The conclusion was that multiple myeloma in Asia is not different from that of Western countries in terms of clinical and cytogenetic characteristics even though there are some minor cytogenetics characteristics observed in certain country that need to be elucidated in future studies. [24] This simple conclusion is very important because there are many ongoing studies on a global scale, especially novel new drugs, in which the participation from Asia is rapidly increasing recently.

Although Asian countries have limited accessibility, or availability, or approval, or affordability of novel drugs in general, each individual country has its own situations and barriers. Many of them are trying to set their standard for the treatment. [25]

1. Torre LA, Bray F, Ferlay J, et al. CA Cancer J CLIN 2015;65:87-108 (IARC GLOBOCAN database) 2012
2. Kang SH, Kim TY, Kim HY, et al. Protective role of CYP1A1*2A in the development of multiple myeloma. Acta Haematol 2008; 119:60–64.
3. Kang SH, Kim TY, Kim HY, et al. Association of NQO1 polymorphism with multiple myeloma risk in Koreans. Korean J Lab Med 2006; 26:71–76.
4. Ozbas-Gerceker F, Bozman N, Gezici S, et al. Asian Pac Cancer Prev 2013;14:5213-5227
5. Jiang N,Zhu X, Zhang H, et al. Clin Lab 2014;60:767-774
6. Lee JH, Lee DS, Lee JJ, et al. Multiple myeloma in Korea: Past, present, and future perspectives. Experience of the Korean Multiple Myeloma Working Party. Int J Hematol 2010; 92:52-57.
7. Huang SY, Yao M, Tang JL, et al. Epidemiology of multiple myeloma in Taiwan: increasing incidence for the past 25 years and higher prevalence of extramedullary myeloma in patients younger than 55 years. Cancer 2007; 110:896-905.
8. Khuhaprema T, Attasara P, Sriplung H, Wiangnon S, Sangrajrang S. Cancer in Thailand. Vol. 7. Bangkok: Ministry of Public Health and Ministry of Education, Thailand, 2013.
9. Park HK, Lee KR, Kim YJ, et al. Prevalence of monoclonal gammopathy of undetermined significance in an elderly urban Korean population. Am J Hematol 2011; 86:752-755.
10. Prevalence of monoclonal gammopathy of undetermined significance: study of 52,802 persons in Nagasaki City, Japan. Iwanaga M1, Tagawa M, Tsukasaki K, et al. Mayo Clin Proc. 2007 ;82:1474-1479.
11. Prevalence of monoclonal gammopathy of undetermined significance in Thailand. Watanaboonyongcharoen P, Nakorn TN, Rojnuckarin P, et al. Int J Hematol. 2012 ;95:176-181.
12. MGUS prevalence in an ethnically Chinese population in Hong Kong. Wu SP, Minter A, Costello R, et al. Blood. 2013 21;121:2363-2364.
13. Lee YG, Bang SM, Lee JO, et al. Five-year follow-up study of monoclonal gammopathy of undetermined significance in a Korean elderly urban cohort. Cancer Res Treat 2015;47:215-220.
14. Kim SJ, Kim K, Kim BS, et al. Clinical features and survival outcomes in patients with multiple myeloma: Analysis of web-based data from the Korean Myeloma Registry. Acta Haematologica 2009;122:200–210.
15. Tsuchiya J, Murakami H, Kanoh T, et al. Ten year survival and prognostic factors in multiple myeloma. Japan Myeloma Study Group. Br J Haematol 1994;87:832–834.
16. Zhang L, Qi JY, Qi PJ, et al. Comparison among immunologically different subtypes of 595 untreated multiple myeloma patients in northern China. Clin Lymphoma Myeloma Leuk 2010;10:197–204.
17. Huang SY, Yao M, Tang JL, et al. Clinical significance of cytogenetics and interphase fluorescence in situ hybridization analysis in newly diagnosed multiple myeloma in Taiwan. Ann Oncol 2005;16:1530–1538
18. Bang SM, Kim YR, Cho HI, et al. Identification of 13q deletion, trisomy 1q, and IgH rearrangement as the most frequent chromosomal changes founding Korean patients with multiple myeloma. Cancer Genet Cytogenet 2006;168:124–132.
19. Lai YY, Huang XJ, Cai Z, et al. Prognostic power of abnormal cytogenetics for multiple myeloma: a multicenter study in China. Chin Med J (Engl) 2012;125:2663–2670
20. Miyakoshi S, Kami M, Yuji K, et al. Severe pulmonary complications in Japanese patients after bortezomib treatment for refractory multiple myeloma. Blood 2006;107:3492–3494.
21. Gotoh A, Ohyashiki K, Oshimi K, et al. Lung injury associated with bortezomib therapy in relapsed/refractory multiple myeloma in Japan: A questionnaire-based report from the "lung injury by bortezomib" joint committee of the Japanese society of hematology and the Japanese society of clinical hematology. Int J Hematol 2006;84:406–412.
22. Koh Y, Bang SM, Lee JH, et al. Low incidence of clinically apparent thromboembolism in Korean patients with multiple myeloma treated with thalidomide. Ann Hematol 2010;89:201–206.
23. Wu SY, Yeh YM, Chen YP, et al. Low incidence of thromboembolism in relapsed/refractory myeloma patients treated with thalidomide without thromboprophylaxis in Taiwan. Ann Hematol 2012;91:1773–1778
24. Kim K, Lee JH, Kim JS, et al. Clinical profiles of multiple myeloma in Asia - an Asian Myeloma Network (AMN) study. Am J Hematol. 2014 ;89:751-6.
25. Hong J and Lee JH. Recent advances in MM:a Korean Perspective. Korean Journal Int Med 2016: in press