Recommendations are ‘call to action’ for African American inclusion in myeloma trials
New guidance that emerged from an FDA and American Association for Cancer Research joint workshop addresses the underrepresentation of African Americans in multiple myeloma clinical trials.
Published in Blood Cancer Discovery, the recommendations are aimed at eliminating racial bias by including more African Americans — who are twice as likely as white individuals to be diagnosed with myeloma — in clinical trials. The recommendations also support using real-world data to better understand the effects of antimyeloma agents among African American patients.
“It is my hope and expectation that these recommendations will serve as a call to action to overcome obstacles to African American participation in clinical trials of novel agents in myeloma,” Kenneth C. Anderson, MD, FAACR, program director of the Lebow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, Kraft family professor of medicine at Harvard Medical School, and head of the Regulatory Science and Policy Subcommittee of AACR, told Healio. “Caregivers, FDA, NIH, industry and patients all helped to develop and strongly endorsed these recommendations, and there is a sincere commitment by the myeloma community to urgently address this issue.”
Barriers to enrollment
Anderson and colleagues developed the final recommendations based on feedback from an FDA-AACR public workshop held in February 2020. The workshop included discussion of draft recommendations proposed by three FDA-AACR working groups with the understanding that, although African Americans represent 20% of the population of patients with multiple myeloma, they represented only 4.5% of patients included in trials for myeloma drug application submissions between 2003 and 2017.
African American enrollment in nine large multiple myeloma clinical trials conducted by NCI Cooperative Groups declined to 13% between 2002 and 2011, from 16.5% in the previous 10-year period.
“Often, African Americans have other medical conditions or comorbidities that preclude their enrollment in clinical trials,” Anderson said. “Clinical trials also may not be open at sites in African American communities and, to date, there have been no standards for assuring their inclusion in trials. And, importantly, there are cultural barriers limiting awareness, access and willingness of African Americans to enroll in clinical trials.
“Our workshop provided a roadmap to address these and other barriers to assure that we learn together the efficacy and side-effect profile of novel agents both before new drugs are FDA approved, as well as after approval when they are used in the African American community setting,” he added.
Americans of African descent also have different disease biology than white patients. For instance, they are more likely than those with European ancestry to have translocations involving the immunoglobulin heavy-chain gene on chromosome 14.
Further, myeloma mortality rates are twice as high among African Americans compared with their white counterparts (5.6 deaths vs. 2.4 deaths per 100,000), according to Anderson and colleagues.
“Tragically, their outcome has not been improved to the extent observed in other patients,” Anderson said. “However, when African American patients were included in new drug registration trials, they did as well or even better than other patients. The FDA and AACR, therefore, convened this workshop with patients, caregivers, NCI, pharmaceuticals and, most importantly, patients, to urgently address this major disparity in development and access to new drugs in myeloma.”
Recommendations
Recommendations from the workshop, co-chaired by Anderson and Nicole Gormley, MD, and Lola Fashoyin-Aje, MD, MPH, both of the FDA, included implementing several changes to the designs of preapproval clinical trials, such as:
- broadening eligibility criteria, as study criteria that reject patients with high blood pressure and kidney disease may disproportionately exclude African Americans;
- requiring trial sponsors to complete a diversity study plan;
- appointing a diversity officer to assist with trial design and recruitment; and
- designing trials to encompass disease subtypes and features seen among African American patients.
“The recommendation to have a prospective plan and goals for accrual of African Americans to clinical trials, including a diversity officer to assure these goals are met, is the most important,” Anderson said. “This will assure awareness, access and enrollment of African American patients in clinical trials to define efficacy and side effects of novel therapies, and ultimately improve patient outcome.”
These recommendations could be extrapolated and applied to increase representation of other subpopulations and underrepresented groups in clinical trials in general, according to Anderson.
“Clinical trials often are not representative of real-world patients, as they may exclude patients with comorbidities, such as hypertension or renal dysfunction,” Anderson said. “The inclusion criteria can be liberalized so that African American patients enrolled are more representative of the real-world patients we treat. Although our workshop addressed this problem specifically focusing on African American patients, broadening inclusion criteria to reflect the real-world patients we treat in the community will improve the drug development paradigm more generally.”
For postapproval clinical trials, Anderson and colleagues recommended researchers, trial sponsors and FDA review divisions:
- conduct prespecified analyses to identify differences among racial and ethnic subpopulations when there is a safety signal or question regarding efficacy;
- pool results across studies to aggregate sufficient data for safety and efficacy analyses among racial and ethnic subpopulations;
- direct stakeholders to devise strategies to overcome clinical, social and socioeconomic impediments to trial access; and
- incentivize inclusiveness.
“It is our responsibility as clinical researchers and caregivers in the cancer care community to proactively focus our efforts on increased understanding of myeloma pathogenesis and treatment in African American patients,” Anderson said. “Our goals are two: to make science count for patients and to treat patients as family. Most importantly, we need to assure that African American patients share the benefits of our continuing treatment advances.”
For more information:
Kenneth C. Anderson, MD, FAACR, can be reached at Dana-Farber Cancer Institute, Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, 450 Brookline Ave., Boston, MA 02215; email: kenneth_anderson@dfci.harvard.edu.
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