African Americans are at a higher risk of multiple myeloma, yet are underrepresented in clinical trials and benefit less from novel therapies for the disease. Research published in Blood Cancer Discovery, proposes a new approach to address racial disparities in drug development for the disease.
African Americans and multiple myeloma (MM)
Researchers analysed data from original NCI Surveillance, Epidemiology and End Result registries. This data suggested that African Americans are not benefitting from advances in MM treatment. Five-year relative survival rates for white Americans diagnosed with MM between 1973 and 2005 increased significantly from 26.3% to 35.0%, while increasing from only 31.0% to 34.1% for African Americans.
Over 30,000 new MM cases are diagnosed every year in the US, and there are over 12,500 deaths from the disease. Incidence rates in African Americans are more than double those seen in white Americans, a trend that also extends to death rate. Despite this, enrolment of African Americans in clinical trials has decreased by 3.5% in the last decade. In total, they make up 20% of people diagnosed with myeloma, but account for only 4.5% of patients in new drug and biological license applications for myeloma between 2003 and 2017.
Problems with drug development for multiple myeloma
Patients with high African ancestry are more likely than European ancestry to have translocations involving the immunoglobulin heavy-chain gene on chromosome 14. Additionally, African Americans are less likely than white Americans to have a depletion of TP53/17p, a hallmark of higher disease risk and shortened survival. These findings highlight that there may be fundamental differences in disease biology between African Americans and white Americans, which could propose an interesting area for new drug development.
It is possible that the data collected from clinical trials does not adequately characterize the safety or efficacy of approved drugs in these patients’ groups. This could be due to the underlying biological and genetic differences between subpopulations. The researchers behind this study argue that a new clinical trial framework needs to be put in place. This will ensure safety, effectiveness and availability of therapies for racial and ethnic minorities.
Reducing racial disparities in drug development
The recommendations that this paper put forward to ensure that clinical trial data is representative of African American populations include:
- Broadening the eligibility criteria when possible. For example, study criteria that reject patients with high blood pressure may disproportionately exclude African Americans. Including these patients may allow researchers to collect more data from subpopulations.
- Requiring trial sponsors to complete a diversity plan, setting targets for enrolling diverse participants.
- Appointment of a diversity officer to assist in trial design and patient recruitment. Trial design should encompass disease subtypes most commonly seen in African Americans, such as the TP53/17p depletion mentioned above for MM.
- Using real-world data to study efficacy and tolerability in subpopulations, where possible, to contribute to the understanding of causal inference.
This framework can be generalised or applied to other subpopulations to improve their representation in the drug development process, and increase reliability of the data collected, to help us better understand how a drug will perform in the population in which they will be used.
The researchers hope that these recommendations will lead to a more inclusive, ‘real-world’ drug development paradigm for multiple myeloma, as well as other diseases more broadly.
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