Dearth of Black/Hispanic Enrollment Noted for FDA Approval Trials in Myeloma

Multiple myeloma clinical trials that are submitted to the FDA for registrational intent appeared to significantly lack representation of Black and Hispanic patients, according to findings from an analysis published in Blood Advances.

The analysis included 19 global trials that enrolled a cumulative total of 10,157 patients. Of these patients, 84% were White, 7% were Asian, 4% were Black, and 4% were Hispanic. Moreover, the age-adjusted hazard ratio (HR) for overall survival (OS) among Black patients vs White patients was 0.89 (95% CI, 0.75-1.02), 0.82 (95% CI, 0.66-1.02) for those in the United States, and 1.31 (95% CI, 0.97-1.77) for the rest of the world. Black patient enrollment was predominantly observed in the United States, where outcomes were noted as being more favorable vs the rest of the world.

“Our analysis suggested differential outcomes among Black patients in the rest of the world compared with African Americans, suggesting that efforts to enroll a more diverse population that is reflective of the U.S. population of patients with multiple myeloma should be directed towards increasing accrual of underrepresented demographic subsets in the U.S.,” the authors wrote. “Such efforts may include increasing accrual of African American [patients] across individual clinical sites as well as increasing the number of sites with high potential to enroll a diverse population.”

The investigators pulled clinical data that were submitted to the FDA from 2006 to 2019. Most clinical studies included in the analysis included patients with relapsed/refractory multiple myeloma, and 3 studies had patients with newly diagnosed disease.

Three percent of patients did not have their race reported. Four patients were American Indian or Alaska Native and 10 were Native Hawaiian or another type of Pacific Islander. For White patients, investigators reported a median age of 68 years, with Black and Asian patients having a median age of 61 years and 66 years, respectively. Hispanic patients had a median age of 68 years. Ethnicity was not reported for 20% of the population.

Of the total population, 17% of patients enrolled on study in the United States and 85% enrolled in other parts of the world. The median age of patients in the United States was 64 years vs 68 years for those across the rest of the world. Additionally, the United States had a higher proportion of Black patients who enrolled (18%) compared with the rest of the world (1%).

Investigators noted that survival in Black and Asian patients was significantly better than White patients. The estimated median OS for White and Black patients was 47.8 months (95% CI, 46.2-49.3) and 63.4 months (95% CI, 47.8-94.4), respectively. Asian patients had a median OS of 46.0 months (95% CI, 42.3-not estimable [NE]). No OS differences were observed between Hispanic and non-Hispanic patients (HR, 0.90; 95% CI, 0.75-1.06).

When assessed by region, patients in the United States appeared to have a better median OS (64.7; 95% CI, 58.4-71.9) vs the rest of the world (45.8; 95% CI, 44.1-47.7; HR, 0.78; 95% CI, 0.69-0.89). Within the United States, Black patients had a longer OS of 81.6 months (95% CI, 63.4-NE) vs White patients (60.4 months; 95% CI, 54.7-67.7; HR, 0.82; 95% CI, 0.66-1.02).

When assessing the rest of the world, estimated median OS was shorter in Black patients (34.4; 95% CI, 23.8-54.1) vs White patients (45.7; 95% CI, 44.0-47.7; HR, 1.31; 95% CI, 0.97-1.77). Furthermore, Asian patients had a better estimated median OS (47.5; 95% CI, 41.0-NE) vs White patients (HR, 0.87; 95% CI, 0.74-1.02). Survival was comparable for Hispanic patients in the United States and the rest of the world vs non-Hispanic patients.

Numerical differences in overall response rate (ORR) were observed among White (66%; 95% CI, 65%-67%), Black (57%; 95% CI, 52%-61%), and Asian patients (75%; 95% CI, 71%-78%). ORR in the United States was 59% (95% CI, 57%-62%) and 67% (95% CI, 66%-68%) in the rest of the world.

Black patients appeared to have 8% lower odds (odds ratio [OR], 0.92; 95% CI, 0.80-1.06) and Asian patients had 11% higher odds of responding to treatment vs White patients (OR, 1.11; 95% CI, 1.01-1.21). Additionally, patients in the United States had 11% lower odds of responding compared with the rest of the world (OR, 0.89; 95% CI, 0.81-0.98). Hispanic patients had an ORR of 67% (95% CI, 68%-71%), 73% (95% CI, 63%-81%), and 65% (95% CI, 60%-70%) overall, in the United States, and in the rest of the world, respectively.

“The U.S. FDA has encouraged broadening of eligibility criteria and adoption of more inclusive enrollment practices to open clinical trials to a diverse participant population reflective of the population that will use the drug if it is approved. Obtaining information about the safety and efficacy of anti-myeloma therapeutics in trials that are reflective of the U.S. patient populations affected is paramount and should be implemented expeditiously,” the authors concluded.

Reference

Kanapuru B, Fernandes LL, Fashoyin-Aje LA, et al. Analysis of racial and ethnic disparities in multiple myeloma U.S. FDA drug approval trials. Blood Adv. Published online February 3, 2022. doi:10.1182/bloodadvances.2021005482