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. 2018 Apr 26;23(9):1076–1078. doi: 10.1634/theoncologist.2017-0592

Representation of Minorities and Elderly Patients in Multiple Myeloma Clinical Trials

Narjust Duma a,*, Tariq Azam b, Irbaz Bin Riaz a, Miguel Gonzalez‐Velez c, Sikander Ailawadhi d, Ronald Go a
PMCID: PMC6192659  PMID: 29700207

Studies have documented underrepresentation of minorities and elderly in oncology clinical trials; however, this issue has not been addressed for some of the most common hematologic malignancies. This article focuses on the representation of minorities and the elderly with multiple myeloma clinical trials over the past 16 years.

Keywords: Hematologic malignancies, Multiple myeloma, Clinical trials, Minorities, Elderly

Abstract

Multiple myeloma (MM) occurs in all races, but the incidence in non‐Hispanic black patients (NHBs) is two to three times higher than in non‐Hispanic white patients (NHWs). We determined the representation of minorities and elderly patients in MM clinical trials. Enrollment data from all therapeutic trials reported in ClinicalTrials.gov from 2000 to 2016 were analyzed. Enrollment fraction (EF) was defined as the number of trial enrollees divided by the 2014 MM prevalence. Participation in MM clinical trials varied significantly across racial and ethnic groups; NHWs were more likely to be enrolled in clinical trials (EF 0.18%) than NHBs (EF 0.06%, p < .0001) and Hispanic patients (EF 0.04%, p < .0001). The median age of trial participants was 62 years, with 7,956 participants (66%) being less than 65 years of age. Collaborations between investigators, sponsors, and the community are necessary to increase access to clinical trials to our minority and elderly patients.

Introduction

Studies have previously documented underrepresentation of minorities and elderly in oncology clinical trials; however, this issue has not been addressed for some of the most common hematologic malignancies. Multiple myeloma (MM) accounts for roughly 1.8% of all malignancies and 10% of hematologic malignancies in the U.S. [1]. The incidence of MM has increased in recent years with a higher incidence in non‐Hispanic black patients (NHBs), representing one of the most commonly diagnosed hematologic malignancies in NHBs [1], [2], [3]. In an analysis of more than 37,000 MM patients, Hispanic patients had a significantly worse median overall survival compared with non‐Hispanic white patients (NHWs; 2.4 vs. 2.6 years; p < .006). Asian patients and NHBs did not have significantly different median overall survivals compared with NHWs [3], [4], [5]. In addition to variation in incidence and mortality by race and ethnicity, MM is predominantly a disease of elderly patients, with an average age of diagnosis of 69 years [1]. Despite this, only one third of trial participants are older than 65 years of age [6].

We sought to determine the representation of minorities and the elderly in MM clinical trials over the past 16 years.

Material and Methods

ClinicalTrials.gov was queried in February 2017 for all completed therapeutic MM trials from 2000 to 2016. Primary search terms included multiple myeloma, adult (16–65), and senior (66+). This search was limited to interventional trials with available results. Clinical trials including other malignancies and stem cell transplants were excluded. Trials with recruitment outside of the U.S. were also excluded, as our objective was to compare clinical trial participants with the U.S. MM population.

Multiple myeloma prevalence and incidence were obtained from the 2014 Surveillance, Epidemiology, and End Results (SEER) program. Because none of these databases included personal identifiers, this analysis received a waiver for the informed consent requirement.

We calculated the enrollment fractions (EFs) for each subgroup. EF was first described by Murthy et al. [7] and is obtained by dividing the number of trial participants by the 2014 SEER MM prevalence. Pearson's chi‐squared test of independence was used to evaluate the relationship between enrollment fractions and various racial or ethnic and age groups. All statistical tests were two‐tailed, and a p value of less than .05 was considered statistically significant. Data analysis was performed using SPSS statistical software (version 22.0, SPSS Inc., Chicago, IL).

Results

From 2000 to 2016, 177 MM trials met the eligibility criteria. After screening, only 78 trials reported race and ethnicity. Of those 78 trials, 52 (66%) were phase II trials, 15 (19%) phase III, and 11 (14%) phase I. Forty‐six trials (59%) were sponsored by the pharmaceutical industry, 25 (32%) by universities or cooperative groups, and 7 (9%) by the National Cancer Institute (NCI). A total of 12,055 patients were enrolled; 84% of participants were NHWs, 8.6% NHBs, 2.8% Asian, 1.8% Hispanic, and 0.1% American Indian or Alaskan Native. Table 1 describes trial participants by race and ethnicity, sex, and age.

Table 1. Participants in all multiple myeloma therapeutic trials, 2000–2016 (n = 28,867).

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a

Sex and age calculation are based on the original 177 MM clinical trials.

Abbreviations: AN, Alaskan Native; MM, multiple myeloma; N/A, no available; SEER, Surveillance, Epidemiology, and End Results program.

Participation in MM clinical trials varied significantly across racial and ethnic groups. NHWs were more likely to be enrolled in clinical trials (EF 0.18%) than NHBs (EF 0.06%; p < .0001) and Hispanics (EF 0.04%; p < .0001). Asian and Pacific Islander participation was similar to NHW (EF 0.19%). Industry‐sponsored trials were less likely to recruit NHB patients compared with trials sponsored by the NCI and universities or cooperative groups (5% vs. 10%; p < .0001; 5% vs. 8.6%; p < .0001, respectively).

The median age of trial participants was 62 years (n = 177 trials), with 68% being less than 65 years of age (p < .0001). Only five trials reported outcomes in patients older than 75 years of age. Enrollment fractions based on age could not be calculated because of differences in age stratification between the databases. A downward trend in the recruitment of elderly patients was noted. The representation of elderly patients decreased from 42% in 2011 to 23% of trial participants in 2016. Phase I trials had the lowest elderly patient recruitment, with 11% of phase I trial participants being ≥65 years of age.

Discussion

The National Institute of Health Revitalization Act of 1993 was created to encourage investigators to increase the representation of women and minorities in clinical trials, but despite efforts led by federal and nonprofit organizations, the recruitment of minorities and the elderly in clinical trials remains low. We observed poor representation of minorities in MM clinical trials, despite their having a higher incidence and mortality from this disease compared with NHWs. We also noted that elderly patients were underrepresented in all MM clinical trials, and a decline in the recruitment of elderly patients was seen over time, despite the development of new and more tolerable agents. These findings aligned with previous studies. Murthy et al. [7] reviewed all NCI cooperative group trials from 1996 to 2002. Results showed that racial and ethnic minorities, women, and the elderly were less likely to enroll in all cooperative group trials compared with NHWs, men, and younger patients.

Low clinical trial enrollment of minority and elderly patients is likely multifactorial, including causes such as health literacy, mistrust in the medical system, lack of access to participating centers, cultural or religious beliefs, and fear of side effects [8]. Expanding inclusion criteria could increase the number and diversity of patients in clinical trials, particularly for elderly patients who are more likely to have comorbidities that would exclude them from participation [9]. Other strategies reported to increase recruitment of minority and elderly patients include the use of bilingual personnel, community outreach, and clinical trials designed to target our aging oncology population [10]. Collaboration between investigators, the NCI, industry, and the community is necessary to overcome these challenges and ensure broad access to trials by underrepresented populations.

There are a number of limitations to our analysis. First, our data were extracted from ClinicalTrials.gov, which relies on investigators and sponsors submitting timely and accurate data about their studies. Next, because of the age reporting differences between the trials database and SEER, we could not calculate enrollment fractions by age group, limiting the understanding regarding the enrollment of these patients.

Future trials should aim to increase the participation of NHB, Hispanic, and elderly patients to improve the knowledge gap that exists regarding efficacy and tolerability of new agents in these subsets of patients.

Footnotes

For Further Reading: David E. Gerber, Ashley M. Lakoduk, Laurin L. Priddy et al. Temporal Trends and Predictors for Cancer Clinical Trial Availability for Medically Underserved Populations. The Oncologist 2015;20:674–682.

Implications for Practice: Despite numerous calls to increase and diversify cancer clinical trial accrual, the present study found that cancer clinical trial activation rates in a safety‐net setting for medically underserved populations have decreased substantially in recent years. The principal reasons for study nonactivation were expenses and an inability to perform the studyrelated procedures, reflecting the increasing costs and complexity of cancer clinical trials. Future efforts need to focus on strategies to mitigate the increasing disparity in access to clinical research and cutting‐edge therapies, which also threatens to hinder study accrual, completion rates, and generalizability.

Disclosures

Sikander Ailawadhi: Celgene, Takeda, Amgen (C/A), Pharmacyclics (RF). The other authors indicated no financial relationships.

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