Dearth of Participation From Black Patients Noted in CAR T Clinical Trials Supporting FDA Approvals

Contemporary Concepts | <b>Contemporary Concepts in Hematologic Oncology</b>

Investigators identified that in pivotal clinical trials supporting FDA approvals of CAR T-cell therapies for patients with hematologic cancer, Black patients were significantly underrepresented.

Notable disparities with regard to Black patients have been observed in CAR T-cell therapy clinical trials that have led to FDA approvals in hematologic cancers, according to findings from a study published in JAMA Network Open.1

Between studies, about 2% to 5% of Black patients were enrolled in clinical trials, received CAR T therapies, and reported efficacy. Using an adjusted prevalence measure, investigators reported that the lowest participation to prevalence ratio was 0.2 for multiple myeloma and 0.6 for large B-cell lymphoma (LBCL). The lowest number of Black patients was observed in the clinical trial that led to the approval of brexucabtagene autoleucel (Tecartus) in mantle cell lymphoma, with only 1 Black patient included.

“The findings of this study suggest that low enrollment of Black persons exists in trials for CAR T therapy and that the disparity is substantial and ongoing, especially for therapies to treat [multiple myeloma]. Efforts should be made to understand and overcome barriers that lead to decreased enrollment of Black participants in clinical trials that include novel, potentially beneficial, and/or curative CAR T therapies in difficult-to-treat hematological malignant neoplasms with otherwise limited treatment options,” Samer Al Hadidi, MD, assistant professor of medicine at the University of Arkansas for Medical Sciences, said in a press release.2

Between August 2017 and March 2021, 5 CAR T products were approved across 7 indications. A total of 1057 patients were enrolled, 746 of whom received CAR T-cell therapies and 729 reported efficacy.

In the study that led to the approval of tisagenlecleucel (Kymriah) in acute lymphoblastic leukemia, patients who were Black were put in a racial category designated as other, “otherwise, their enrollment was specified mainly in the demographic subgroups information available under the FDA product labeling information.”

Investigators noted that most of the studies included in FDA approvals did not report the proportions of racial and ethnic groups. Eighteen Black patients with diffuse LBCL who were treated with CAR T-cell therapy reported efficacy per disease category. Additionally, in one CAR T-cell therapy approval study for multiple myeloma, only 6 Black patients participated, comprising 6% of the total patient population.

“The incidence of [multiple myeloma] is more than 2 times higher among Black persons than among non-Hispanic White persons,” the investigators wrote. “Black patients with [multiple myeloma] face multiple disparities, including lower use of hematopoietic stem cell transplantation, palliative care, and novel therapeutics, which may result in worse outcomes. Lack of access to novel therapies that disproportionately affect Black persons may result in further widening of the existing established disparities.”

On April 13, 2022, the FDA initiated a plan to increase clinical trial diversity by employing the Race and Ethnic Diversity Plan.3 This has gone into effect for companies submitting applications for investigational new drugs, biologics license application, or investigation device exemption. This new plan recommends that companies define their enrollment goals for underrepresented populations so that they may be a part of pre-specified protocol objectives.

References

  1. Al Hadidi S, Schinke C, Thanendrarajan S, Zangari M, van Rhee F. Enrollment of black participants in pivotal clinical trials supporting US Food and Drug Administration approval of chimeric antigen receptor-T cell therapy for hematological malignant neoplasms. JAMA Netw Open. 2022;5(4):e228161. doi:10.1001/jamanetworkopen.2022.8161
  2. Study: Black patients underrepresented in pivotal CAR T-cell trial. News Release. Regulatory Affairs Professionals Society. April 20, 2022. Accessed April 21, 2022. https://bit.ly/36yhrEa
  3. FDA recommends sponsors plan to include race, ethnicity in clinical trial design. News Release. Regulatory Affairs Professionals Society. April 13, 2022. Accessed April 21, 2022. https://bit.ly/3jXKILt