ASCO 2019 | Disparities in multiple myeloma care

During the 2019 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, US, a session was held on disparities in multiple myeloma (MM) care. Siddhartha Ganguly, University of Kansas Cancer Center, first presented disparaties associated with living in a rural location in America. Sham Mailankody, Memorial Sloan Kettering Cancer Center, moved on to describe the global differences in patient treatment, and finally Sikander Ailawadhi, Mayo Clinic, looked at the disparities from a racial perspective.¹

The MM Hub were delighted to interview both Siddhartha Ganguly and Sikander Ailawadhi on disparities in MM care. Their interviews can be found at the bottom of this article, in the expert interview section.

Rural America

Prof. Ganguly first stated that we need to accept that there is an issue within the United States (US) regarding access to quality healthcare. Patients in rural locations;

• Have a lack of access to screening tests,
• Are less likely to be able to access the therapies proposed by current guidelines,
• Are less able to access clinical trials

There are few studies in MM that have examined the differences in patient outcome between rural and urban populations. Prof. Ganguly presented the available data, including one retrospective study that showed, of 81 patients in New Mexico, classified to rural or urban, median overall survival (OS) significantly varied (P < 0.001) between 39.03 months (18.96-57.99) in rural locations and 68.99 months (25.95–90.02) in urban locations. Additionally, urban patients were more often diagnosed whilst asymptomatic with rural patients more commonly diagnosed at a more advanced stage of disease, indicating they waited longer before seeking medical attention.²

Another study from the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Sciences, found the following environmental factors were associated with the development of MM; being raised in a rural area, raising cattle or cotton and exposure to pesticides, insecticides or herbicides.³

There are data regarding the stem cell transplantation utilization rate (STUR), in relation to race, but no studies have yet reported the STUR in rural versus urban populations. The Center for International Blood and Marrow Transplant Research (CIBMTR) reported that Hispanic and non-Hispanic black patients have a lower STUR compared to non-Hispanic white patients, though race did not impact patient outcomes in this study. The authors of this study concluded that an emphasis should be placed on groups where transplant is under-utilized.⁴ Another study by Keshav Rao and colleagues found that patients from rural areas who received an autologous stem cell transplant (ASCT) for a hematological malignancy had an increased relative risk of death (risk: 1.18, P = 0.16) compared to urban populations.⁵

In a personal survey, 12 questions were sent to oncologists. The results showed;¹

• Nearly all used a triplet induction therapy in patients with newly diagnosed MM (NDMM)
• 50-60% had referred patients for ASCT
• Issues in rural areas were distance and transportation and low accrual into clinical trials

A JAMA network paper studying cancer patients located in rural areas, containing 19.4% of patients from rural areas, did not find significant differences on OS or progression-free survival (PFS) comparing Hispanic, non-Hispanic white and non-Hispanic black patients. This study concluded that if treatment was uniformly provided across rural and urban locations, the disparity in cancer outcomes may be alleviated.⁶ A study by Jacob Orme and colleagues, found distance from a National Cancer Institute center influenced the OS of patients with MM.⁷

Looking forward, Prof. Ganguly stated that many factors should be considered when planning a study. These included age, socio-economic status, the type of insurance the patient has, their education level, the stage of disease at diagnosis, travel distance to treatment centers, family dynamics, amongst others.

He concluded that increasing awareness, allocating healthcare carefully and initiating discussions are needed to change the current disparity. “Your zip code in North America is as important as your DNA.”

Global disparities¹

Dr Mailankody began his talk by highlighting the differences between global populations, in relation to the occurrence of MM and monoclonal gammopathy of undetermined significance (MGUS). The incidence of MM and MGUS is two-fold higher in the African-American population and lower in the Asian population, though he noted that these differences may be attributable to a lack of reporting systems and diagnostic facilities.^8-9

Dr Mailankody then highlighted how worldwide access varies, in relation to:

• Pathology services: there is a significant difference. In sub-Saharan Africa (population 771.2 million), there are, on average, 606 pathologists which equates to 1 per 1.3 million population. In 6 countries, there is only one pathologist for the entire population. This contrasts with the US, where 1 pathologist is available per 20,638 population¹⁰
• Radiotherapy services: there are 2,113 centers in the US, but 74 countries have less than 5¹¹
• Medical oncology: in a survey of 93 countries, 8 countries had no oncologists. In 29% of countries, there was one oncologist per 1000+ cancer patients, predominantly in Africa¹²
• It is clear from this data that there is a global difference in access to cancer care, with low- and middle-income countries suffering the most.

In myeloma specifically, Dr Mailankody presented data on the availability of lenalidomide and bortezomib in 196 countries. Lenalidomide is approved in 37% of the countries (n = 73) whilst bortezomib is available in 53% (n = 103). With this data, Dr Mailankody concluded that approval of drugs does not necessarily mean access in many cases.¹³

The STUR was also shown, globally, to be very low in many countries, with less than 150 transplants per 10 million in most of south America, Russia and parts of Asia, and with no usage in much of Africa. In India, the rate of stem cell transplant in major centers is approximately 20%.¹³ In conclusion, lack of infrastructure, poverty and a lack of insurance limits the access most patients have to novel agents and stem cell transplant.

Dr Mailankody then moved on to discuss the ways that we can work to remove these limits including by collaborating and providing training. Dr Mailankody noted the importance of educating and training colleagues from low and middle income countries through partnerships between professional organizations and academic centers, as well as designing collaborative clinical trials.

He also noted that one way to increase access to high-quality care, is to use non-cryopreserved stem cells for autologous transplant which costs 15% less than the traditional method. Another option, is to increase the money that governments are spending on healthcare, and to provide universal basic healthcare to all. He concluded that this is an approach that will require global governments to work together and address the fundamental issues.

Racial disparities

Assoc. Prof. Ailawadhi provided the final talk of the session, presenting the racial disparities in MM care. He began by defining race as a person’s self-identification with one or more social groups (e.g. white, black, Asian, American Indian and so on), whist ethnicity was defined as a group of people who identify with one another based on common ancestral, social, or cultural experiences (e.g. Hispanic or non-Hispanic). This is important as it adds a level of complexity to defining race, within this context.

Racial differences in MM:

1. Age: when comparing age at diagnosis between the white, African-American, Asian and Hispanic population, there is a statistically significant difference (P < 0.001) with a median age at diagnosis of 71 vs 66 vs 69 vs 65 in a study of 37,963 patients.¹⁴
2. Complications at and after diagnosis. There were significant differences in all complications by race, with a higher incidence of all complications, including fractures, anemia and renal dysfunction in black patients (P < 0.02).¹⁵
3. Disease biology: in a comprehensive genomic analysis, three additional candidate myeloma genes were identified, due to the lack of African-Americans in current datasets. The authors concluded that there are molecular differences between Caucasian and African-American MM and that defining these in the African-American population is crucial to better manage the disease clinically¹⁶
4. Healthcare access and delivery: it was noted that there are socio-cultural determinants of healthcare access including the patient lifestyle, community environment and work-life balance
5. Survival: in a study by Sikander Ailawadhi and colleagues, it was shown that median OS was different between racial groups with Hispanics having a significantly worse OS compared to whites (P = 0.006)¹⁴. Also, the increase in survival rates of white patients with MM has not been matched at the same level in black patients, over the last 30 years, with the authors of this study stating this may be to unequal access.¹⁷
6. Use of stem cell transplant: within the MM landscape, there are numerous data to show the racial differences in STUR. Comparing STUR in African-Americans to the Caucasian population, the age-adjusted odds ratio is higher for Caucasians (OR: 1.75, 95% CI, 1.64–1.86, P < 0.001)^18. Additionally, STUR is the lowest in the Hispanic population and has had the lowest increase over time.⁴

1. Novel therapeutic agent access: interestingly, the use of different novel agents varies based on racial background (Table 1)¹⁹

Table 1: incidence of use, by therapeutic agent, within first year of M diagnosis, by race¹⁹

	White (n = 3574)	Hispanic (n = 531)	African-American (n = 945)	Asian (n = 288)	Adjusted P value
Lenalidomide	22.8%	23.7%	19.4%	21.2%	< 0.01
Thalidomide	18.3%	27.9%	18.7%	28.5%	< 0.01
Bortezomib	12.8%	8.3%	11.9%	7.6%	< 0.01

• Lenalidomide: lower utilization in African-Americans
• Bortezomib: lower utilization in Asians
• Median time to first bortezomib dose: highest in Hispanics (median days = 117)
• In addition, access to novel agents may be influenced by insurance status
• Factors that may cause these barriers include referral bias, cultural barriers, a lack of coordinated care, differences in decision-making and differences in the cost of treatment.

1. Clinical trials. There is a disparity in the recruitment of different races to clinical trials in cancer: non-Hispanic white patients make up the predominant race (83.4%) compared to African Americans (5.9%), Asian/Pacific islander (5.3%), Hispanic (2.6%), other (2.5%) and American Indian/Alaskan native (0.3%)²⁰

Conclusion

All three speakers noted that when racial, geographical and socioeconomic factors were removed from the equation, the outcomes and responses of patients were the same, concluding that we need to work to increase access to novel treatments, stem cell transplantation and accrual to clinical trials.