Attaining Health Equity: Practices for Decreasing Racial Disparities in Multiple Myeloma Therapies

While there has been great progress in Multiple Myeloma (MM) treatment, studies indicate that African Americans are not benefitting from such advances.(1) Barriers to clinical trial participation are at the root of this disparity.

MM disproportionately affects African Americans, with incident rates in this racial group more than double those seen in whites (15.9 vs.7.5 cases per 100,000).(1) MM is also the most common blood cancer among African Americans.

Clinical trials are vital to revealing the efficacy of therapies for all patients with MM. Many researchers discount or do not realize the importance of recruiting and enrolling African Americans diagnosed with MM for trials, especially for novel therapies.(1) However, African American participation in trials helps assure that new treatments are effective for everyone affected by the disease.

African Americans are underrepresented in MM clinical trials. While they comprise 13% of the entire population in the United States, African Americans make up only 5% of trial populations.(1) 

Current recruitment and enrollment practices for MM clinical trials include important eligibility criteria that limit African Americans’ participation in clinical trials. Two such eligibility criteria are failure to meet trial-specific hematologic laboratory criteria and failure to meet treatment-related criteria.(2)

Failure to meet trial-specific hematologic laboratory criteria can restrict African Americans’ participation in MM clinical trials if they have a low absolute neutrophil count (ANC) seen as abnormal (neutropenia). Benign ethnic neutropenia (BEN) is a well-established, inherited trait seen primarily in people of sub-Saharan African descent. Although BEN is well known and does not affect immune system function, researchers and clinicians continue to use an ANC reference range that is not representative of the entire population and disproportionately restricts the eligibility of African Americans for MM clinical trials.(3)

Failure to meet treatment-related criteria can also restrict African Americans’ participation in MM clinical trials.2,4 A 2020 analysis of 639 newly diagnosed MM patients found that African Americans were less likely than whites to have received important standard triplicate therapies and first-line autologous stem cell transplant, preventing them from qualifying for trial inclusion.(4)

Clinical trial participation is also limited by trial sites. Often, trial sites are housed in urban medical centers far away from both African American patients living in rural areas, as well as those living in smaller cities and towns not near the trial site.   

Furthermore, many African Americans, are hesitant to participate in clinical trials, possibly due to cultural barriers and historical abuses such as the Tuskegee syphilis study and the theft of Henrietta Lacks’s cells. This hesitancy is a recruitment issue that must also be addressed.

One of the reasons why it’s important to encourage African Americans to enroll in MM trials and allow them to do so, is because their genetic and biological response to therapies may differ from other population groups.(5,6) Because of such differences, more African Americans need to be enrolled in clinical trials. Otherwise, underrepresentation in clinical trials may lead to therapies being developed and distributed that are less effective for African Americans, lowering their chances of achieving remission.

If MM therapies are to work for everyone, eligibility criteria in MM clinical trials need to be broadened to collect more data in racial and ethnic subpopulations. This sentiment is supported by the FDA, which recommends developing diversity plans and broadening eligibility criteria when scientifically appropriate to improve African Americans’ clinical trial participation.(7)

Ideally, trial design will support increasing and retaining the numbers of African Americans in MM trials by enacting inclusive recruitment and enrollment policies. Trial teams will develop strategies to enroll, accrue and retain appropriately diverse populations, including approaches to overcome cultural barriers.

There are numerous strategies one can enact to improve African Americans’ trust and encourage their enrolment in MM clinical trials(8):

• Reach out to trusted stakeholders working within the African American community; have a conversation to let them know where the study is being conducted and what it is about.

• Make connections with community health centers and talk to patients about the design and planning of studies, the clinical trials, and their potential benefits.

• Appeal to physicians in the community; ask them to recommend clinical trials when appropriate for their patients.

• Cultivate internal Diversity, Equity, and Inclusion committees to increase the diversity of investigators, research coordinators, and research associates within clinical trial teams.

One can also improve representation of African Americans in clinical trials by bringing required activities to the participants. For example, partnering with community sites such as pharmacies, doctor’s offices, and health clinics can provide easier access to trial activities for patients. Clinical trial teams could also work together with trial sponsors to fund patient transportation, allowing MM trials to recruit from a larger and more diverse population. Additionally, major trial centers could partner with local sites, giving participants the opportunity to enroll in a trial in their hometown.(8) 

Along with making trial sites more accessible, trial teams are advised to work to broaden eligibility for clinical trials whenever possible and appropriate.(1,7) For African American patients with MM, this could mean inclusion in a trial despite having BEN or not receiving standard triplicate therapy and first-line autologous stem cell transplant. Sponsors of MM clinical trials should determine the significance of baseline therapies to the external validity of a drug or treatment regime. If deemed significant, sponsors could collaborate with a patient’s physician(s) to provide these therapies in early phase drug development.

In summary, broadening trial inclusion criteria would certainly help pave the way for more African American trial participation. However, to be effective, recruitment practices must also emphasize proportionate representation. Changing these discriminatory practices may seem like a difficult task but understanding the importance of multiracial/multiethnic representation and learning strategies to increase recruitment is vital.

To overcome trial participation barriers for African Americans, clinical trial teams must be willing to adopt and enact inclusive recruitment and enrollment practices aimed at increasing African American participation in MM clinical trial populations. Racial and ethnic disparities in cancer outcomes for MM could be eliminated if every patient had equal access to standard treatment, and clinical trials.(9)

Clinical trial teams, working in consort with African American patients, sponsors, and other health care professionals, have the leverage to upend racial disparities in MM therapies. Enact these strategies to change outreach and eligibility practices to increase the numbers of African Americans in your MM clinical trial populations.

References

1.      Gormley N, Fashoyin-Aje L, Locke T, Unger JM, Little RF, et al. Recommendations on eliminating racial disparities in multiple myeloma. Blood Cancer Disc 2021; 2:119-24. doi: 10.1158/2643-3230.BCD-20-0123.

2.      Kanapuru B, Fernandes AB, Ershler R, et al. Eligibility criteria and enrollment of a diverse racial and ethnic population in multiple myeloma clinical trials. Blood (2023) 142 (3): 235–243. doi: 10.1182/blood.2022018657.

3.      Merz LE, Achebe M. When non-whiteness becomes a condition. Blood 2021) 137 (1): 13–15. doi: 10.1182/blood.2020008600.

4.      Deman BA, Jasielec J, Langerman SS, Zhang W, Jakubowiak A, Chiu B. Racial differences in treatment and outcomes in multiple myeloma: a multiple myeloma research foundation analysis. Blood Cancer J. Aug; 10(8): 80. doi: 10.1038/s41408-020-00347-6.

5.      Baughn LB, Pearce K, Larson D, Polley MY, Elhaik E, Baird M, Colby, C, Benson, J, et al. Differences in genomic abnormalities among African individuals with monoclonal gammopathies using calculated ancestry. Blood Cancer J 2018; 10. doi: 10.1038/s41408-018-0132-1.

6.      Waxman AJ, Mink P, Devesa SS, Anderson WF, Weiss BM, et al. Racial disparities in incidence and outcome in multiple myeloma: a population-based study.  Blood 2010; 116[25]: 5501-5506. doi: 10.1182/blood-2010-07-298760.

7.      U.S. Department of Health and Human Services. Diversity Plans to Improve Enrollment of Participants from Underrepresented Racial and Ethnic Populations in Clinical Trials Guidance for Industry. DA-2021-D-0789. Accessed December 4, 2023.

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/diversity-plans-improve-enrollment-participants-underrepresented-racial-and-ethnic-populations

8.      Florencehc.com. FDA guidance for diversity in clinical trials: what you need to know blog. Apr 16, 2023. Accessed December 4, 2023.

https://florencehc.com/blog-post/fda-guidance-for-diversity-in-clinical-trials-what-you-need-to-know/

9.      Sengupta R, Honey K. AACR Cancer Disparities Report 2020. Cancer Epidemiol Biomarkers Prev (2020) 29 (10): 1843. doi: 10.1158/1055-9965.EPI-20-0269.