In a workshop held by the FDA in partnership with the American Association for Cancer Research (AACR) on February 13, 2019 in Wardman Park, Washington D.C., researchers from various institutions discussed the current state of African American outcomes and treatment in multiple myeloma trials and the clinical implications.
“Although there’s still this disparity, the rate of change in the right direction seems to be similar ,” Kenneth C. Anderson, MD, FAACR, program director for the Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics at the Dana-Farber Cancer Institute, said of the findings.
In an analysis based on preliminary FDA findings that suggested there was limited enrollment of African Americans in multiple myeloma clinical trials, researchers looked to see if there were differences in outcomes due to race and if there are differences in screen failure rates that contribute to differences in enrollment. Additionally, they looked to address if eligibility criteria are restrictive for certain demographic subgroups.
Statistics From the FDA
The presenters, Laura Fernandes, PhD, and Bindu Kanapuru, MD, of the FDA, summarized that enrollment of black patients was significantly less in their pooled dataset compared to white patients. Additionally, there were no conclusive differences in the different racial categories in regard to overall response rate, progression-free survival, and overall survival.
Moreover, more black patients failed to meet the screening criteria than their white and Asian study counterparts. In regard to the screen failure analysis, Kanapuru said, “In general, fewer black patients were screened compared to whites and Asians. Second, among those who were screened for enrollment onto the multiple myeloma clinical trials, there is a trend towards higher screen failure rates for blacks compared to white.”
Notably, Kanapuru indicated that the FDA has several ongoing initiatives and also published several guidances in an effort to expand eligibility criteria.
The Importance of Real-World Evidence
Moreover, in an evaluation of characteristics and outcomes of patients with multiple myeloma from an EHR-derived database, Kathleen Maignan, MSN, NP, from Flatiron Health, suggested that researchers were able to assess outcomes in patient subgroups that are likely to have lower representation or even be excluded from trials. Unadjusted results from the database indicated that black patients have similar or better outcomes when compared to white patients. However, adjusting for age and sex minimized this difference, especially for overall survival.
“While real world data does have more African American patients, the representation still is not the same,” Maignan said.
The research also suggested that black patients have a higher comorbidity burden, which could minimize their consideration for future trials. “So, when we look at future directions, given the higher comorbidity burden amongst black patients, we see a potential to conduct future work in this subgroup which may have an unmet need,” Maignan said. “We also look forward to opportunities to further investigate genomic differences by race as we expand our clinical genomics database and availability there.”
Representing the Dana-Farber Cancer Institute
Furthermore, covering the scope of the issues, Nikhil C. Munshi, MD, of the Dana-Farber Cancer Institute, indicated that race has significant influence on outcomes and overall survival, as well as age within the different racial groups. Physiological and microenvironment parameters may also play a role with racial differences on outcomes in myeloma according to the researcher. Additionally, traditional prognostic factors may still have variability across racial differences.
“So, the critical question now is to study the biological basis for these differences using genomics and all of the different technologies that are directly available to us,” Munshi said. Moreover, he recommended that researchers studying patients with multiple myeloma evaluate the impact of race on therapeutic intervention and their PK/PD, as well as disease sensitivity compared to disease resistance.
Biological and Genomic Differences of Multiple Myeloma
Looking at biological and genomic differences of multiple myeloma, Shaji K. Kumar, MD, from the Mayo Clinic Cancer Center, Kumar indicated that MGUS is 2-3 times more common in African Americans, which correlates with the fact that myeloma is 2-3 times more common as well. Additionally, he found that there was a trend to earlier age of onset MGUS in blacks compare to whites, with the disparity in prevalence between blacks and whites being most striking within the 40-49 age group (3.26% vs 0.53% ; P = 0.0013).
“I think we want to think about this differently,” said Kumar. “We are talking about a group of patients who get diagnosed about 10 years younger, who have better biology because of the fundamental underlying genetic differences, despite having advancements at diagnosis they tend to do better, so really the actual setting should be the African Americans should be doing a lot better than what they’re doing now.”
The researcher then indicated that important role for screening in the African American patient population, especially with research showing that earlier screening would be beneficial in multiple myeloma. By treating them earlier, he presents the idea that their outcomes could actually be even better than the Caucasian patients. Additionally, Kumar indicated that the access to therapy, specifically stem cell therapy, needs to be addressed.
In the final presentation, Ajay K. Nooka, MD, from the Winship Cancer Institute of Emory University, discussed how to increase minority accrual in myeloma clinical trials through experiences and lessons learned within his own institution. At the system level, a lack of clinical trial infrastructure and insurance were the most prevalent barriers. At the individual level, a lack of trust, fear related to research participation, inadequate information about research, and access/convenience of participation all presented as barriers for clinical trial enrollment.
He listed some solutions that physicians within his institution brought attention to, including:
- Creating community advisory boards
- Delivering culturally targeted education programs
- Partnering with community-based organizations serving the Black community
- Improving access to clinical care and support services
- Myeloma awareness events
- Faculty diversity
- Leadership buy-in
- Addressing the problem
Following the presentation of the state of the science at the workshop, working groups presented recommendations for how to combat the addressed disparities in African American representation within multiple myeloma clinical trials.
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