Better Minority Enrollment Needed in UK Multiple Myeloma Trials

Rakesh Popat, MBBS, FRCPath, PhD

More racial diversity in clinical trials in the UK is needed to better reflect patient population for multiple myeloma.

A team, led by Rakesh Poat, MBBS, FRCPath, PhD, University College London Hospitals, examined the ethnic diversity of multiple myeloma clinical trials in the UK over the course of 18 years in data presented at 2021 American Society of Hematology (ASH) Annual Meeting & Exposition.

Multiple myeloma incidence rates can vary greatly by ethnicity. For example, Black patients are approximately twice as likely to developed the disease in comparison with White or Asian patients (Black: White males 2.9:1, females 2.2:1).

The Data

In 2015, the National Cancer Registration and Analysis Service (NCRAS) reported the incidence of multiple myeloma by ethnicity in England over 10 years was 85.5% for White patients, 5.4% Black, 3.6% Asian, and 1.9% other.

However, ethnic minorities are often underrepresented in clinical trials, likely partially because of socio-economic factors. It is unknown whether these disparities exist in state funded health care systems where access to care if free and ideally equitable.

In the study, the investigators collected data on ethnicity, baseline demographics, progression-free survival (PFS), and overall survival from patients enrolled into 1st line UK academic transplant eligible (TE) and transplant non-eligible (TNE) – Myeloma IX, XI and XIV trials, and at 1st relapse – Myeloma X and XII clinical trials between 2003-2021 across 120 centers. There were a total of 7291 patients enrolled across 5 different randomized controlled trials with an ethnic distribution of 93.8% White, 2.2% Black, 1.8% Asian, 1.6% other, and 1.6% unknown.

However, the Myeloma XII and XIV (FiTNEss) trials are currently enrolling, while the remainder have closed.

The studies were designed to have permissive eligibility criteria so they were able to enroll as close to real world patients as possible.

The investigators summarized baseline characteristics and used chi-squared tests to make comparisons.

They also made comparisons with population-level data using one-sample chi-squared tests and estimated survivor functions using the Kaplan-Meier method, which were compared using the logrank test.

Finally, they used Cox proportional hazards models with suitable interaction terms to test for heterogeneity.

Disparities

The disparities between the different races was clearer in TNE studies Myeloma IX non-intensive: White 97.4%, Black 1.3%, Asian 0.4%; Myeloma XI non-intensive: White 94.5%, Black 1.8%, Asian 1.6%, Myeloma XIV: White 94.2%, Black 0%, Asian 3.2%).

However, the different to the incidence of myeloma cases across the UK with the difference was most pronounced in TNE trials (TE trials (observed vs NCRAS, P <0.0001); TNE trials (observed vs NCRAS, P <0.0001); 1st relapse trials (observed vs NCRAS, P = 0.035)).

The enrollment distribution was consistent by ethnicity over the course of 18 years, with no change in diversity over time despite there being an increase in the UK in the non-White population.

In the Myeloma IX trial, there was no significant difference in age at enrollment, but the performance status in Black patients was worse than non-Black individuals (P = 0.045). However, there were fewer cytogenetic high risk Black patients (P = 0.007), as well as less ISS 1 Black patients compared to non-Black patients (P = 0.0416).

There were no differences in demographics by ethnicity in the Myeloma XI trial.

Outcomes were similar within each trial for overall survival and PFS, with an improvement in overall survival shown over time from Myeloma IX to the Myeloma XI trial with the incorporation of novel agents (median OS MRC-Myeloma IX: 48 months vs. median OS NCRI Myeloma-XI: 70 months, P < 0.0001).

There was also no evidence of any heterogeneity of effect to ethnicity (P = 0.456), which suggests all ethnic subgroups benefited from the improvement in overall survival.

“Enrollment of ethnic minorities into academic clinical trials in the UK was below that expected despite enrolling from >100 geographically spread sites and intended equitable access to healthcare,” the authors wrote. “All ethnic groups derived an OS benefit from novel agents within trials that were not otherwise routinely available; however, a substantial proportion of ethnic minorities were not enrolled particularly TNE patients, thereby limiting their survival gains.”

The study, “Enrolment and Outcomes of Ethnic Minorities with Multiple Myeloma Treated in UK Myeloma Research Alliance (UK-MRA) Clinical Trials over 18 Years,” was published online by ASH.