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Do Not Cut and Paste: Improving Clinical Trial Representation

Christopher Flowers, MD, MS, FASCO

Division Head Division of Cancer Medicine

Chair, Professor Department of Lymphoma/Myeloma

MD Anderson Department of Lymphoma/Myeloma

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Disclosures

Consultant: Abbvie, Bayer, BeiGene, Celgene, Denovo Biopharma, Foresight Diagnostics, Genentech/Roche, Genmab, Gilead, Karyopharm, N-Power Medicine, Pharmacyclics/Janssen, SeaGen, Spectrum.

Stock Options: Foresight Diagnostics, N-Power Medicine

Research Funding: 4D, Abbvie, Acerta, Adaptimmune, Allogene, Amgen, Bayer, BostonGene, Celgene, Cellectis EMD, Gilead, Genentech/Roche, Guardant, Iovance, Janssen Pharmaceutical, Kite, Morphosys, Nektar,Novartis, Pfizer, Pharmacyclics, Sanofi, Takeda, TG Therapeutics, Xencor, Ziopharm, Burroughs Wellcome Fund, Eastern Cooperative Oncology Group, National Cancer Institute, V Foundation, Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research

​

MD Anderson Department of Lymphoma/Myeloma

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Enrollment of in Pivotal Clinical Trials Supporting US FDA Approval Do Not Reflect Disease Demographics

Hadidi et al. JAMA Netw Open 2022

Participation to Prevalence Ratio for Black Participants Enrolled in Clinical Trials Supporting CAR T Approvals

Birhiray and Birhiray Blood Adv 2023

  • In pivotal trials leading to approval of immune checkpoint inhibitors, Black patients constituted <4% of enrollees
  • A study of 85 pharma-sponsored trials and 273 SWOG trials including 93,825 patients and 15 cancer types (2008 – 2018) found underrepresentation of Black patients in pharma sponsored trials compared with SWOG trials (2.9% vs 9.0%) across individual cancer types.

MD Anderson Department of Lymphoma/Myeloma

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Enrollment of Black Participants in Pivotal Clinical Trials Supporting US FDA Approval of CAR T Cell Therapy for Hematological Neoplasms

Hadidi et al. JAMA Netw Open 2022

Therapy and study

Approval date

Indication

Enrolled (n)

Asian

Black

White

Other

Black participants who received product n (%)

Tisagenlecleucel

Maude et al N Engl J Med 2018

8//2017

≤25 y with B-ALL ≥ 2 relapse

88

11%

NR

74%

15%

NR

Tisagenlecleucel

Schuster et al N Engl J Med 2019

5/2018

Adult patients with rrLBCL ≥2 lines therapy

160

NR

NR

NR

NR

2 (3%)

Axicabtagene ciloleucel

Locke et al N Engl J Med 2022

10/2017

Adult patients with rrLBCL ≥2 lines therapy

111

NR

NR

NR

NR

4 (4%)

Axicabtagene ciloleucel

Ghione et al Blood 2022

3/2021

Adult patients with rrFL ≥2 lines therapy

123

NR

NR

NR

NR

3 (4%)

Brexucabtagene autoleucel

Wang et al N Engl J Med 2020

7/2020

Adult patients with rrMCL ≥2 lines therapy

91

NR

NR

NR

NR

1 (2%)

Lisocabtagene maraleucel, Abramson et al Lancet 2020

2/2021

Adult patients with rrLBCL ≥2 lines therapy

344

4%

5%

86%

6%

12 (5%)

Idecabtagene vicleucel

Munshi et al N Engl J Med 2021

3/2021

Adult patients with rr myeloma ≥2 lines therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody

140

2%

6%

81%

4%

Unknown

(7%)

6 (6%)

MD Anderson Department of Lymphoma/Myeloma

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Birhiray and Birhiray Blood Adv 2023

MD Anderson Department of Lymphoma/Myeloma

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D: diversity officer for clinical research studies

Birhiray and Birhiray Blood Adv 2023

Responsibilities of a diversity officer:

  1. Prospectively develop an achievable, flexible and monitorable DEIA plan with accrual goals for diverse populations
  2. Establish infrastructure to monitor and adjust recruitment efforts prospectively, including, outside the United States, particularly in African countries where the infrastructure may not already exist
  3. Identify impediments to meeting accrual goals at the micro and macro levels
  4. Develop culturally appropriate study materials to promote accrual
  5. Identify scientific questions and study design solutions that improve methods of prevention, diagnosis, and therapy
  6. Advise the study sponsor(s), Pis, and the steering committee on potential challenges and solutions.

​

Qualifications of the diversity officer include training in:

  1. Cancer research
  2. cultural awareness, sensitivity, appropriateness, and diversity;
  3. Historical factors precluding potential enrollment in clinical trials
  4. Leadership

MD Anderson Department of Lymphoma/Myeloma

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Impact of Demographics and Neighborhood Socioeconomic Variables on Clinical Trial Participation in Non-Hodgkin Lymphoma

Participation Rate

White

20

80

100

Asian

Hispanic

Other

Black

Asian

Hispanic

Other

Black

40

0

10

30

40

50

60

20

Diffuse Large B-cell Lymphoma

Age

Self-reported Race

Area Deprivation Index

60

Nze et al. Blood Adv 2024

  • In center with a robust clinical trial infrastructure and a strong culture of trials, clinical trial enrollment is high across demographics
  • Race, gender, socioeconomic variables were not predictors of trial participation, whereas age was

MD Anderson Department of Lymphoma/Myeloma

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NHL Patient Perspectives: �Barriers�Facilitators�for Trial�Participation�

​

Total�(N=257)

MDACC�(N=191)

Harris Health�(N=66)

Sex

​

​

​

Male

139 (54.1%)

114 (59.7%)

25 (37.9%)

Female

116 (45.1%)

76 (39.8%)

40 (60.6%)

Missing

2 (0.8%)

1 (0.5%)

1 (1.5%)

Age

​

​

​

Mean (SD)

58.8 (13.6)

61.2 (13.6)

53.1 (11.9)

Median [Min, Max]

61.0 [19.0, 88.0]

64.0 [19.0, 88.0]

55.0 [22.0, 80.0]

Missing

36 (14.0%)

35 (18.3%)

1 (1.5%)

Race / Ethnicity

​

​

​

Non-Hispanic White

79 (30.7%)

72 (37.7%)

7 (10.6%)

African American

44 (17.1%)

35 (18.3%)

9 (13.6%)

Hispanic/Latinx

128 (49.8%)

79 (41.4%)

49 (74.2%)

Asian/Pacific Islander

0 (0%)

0 (0%)

0 (0%)

Native American

1 (0.4%)

1 (0.5%)

0 (0%)

Other, specify

2 (0.8%)

2 (1.0%)

0 (0%)

Missing

3 (1.2%)

2 (1.0%)

1 (1.5%)

MD Anderson Department of Lymphoma/Myeloma

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Patient Perspectives: �Developing Interventions

 

 

 

Qualitative Data Collection

Quantitative Data Collection

Qualitative Data Analysis

Quantitative Data Analysis

Merge Qualitative & Quantitative Findings

Integrated Interpretation

 

 

 

Quantitative:

    • Identifying prevalent attitudes about clinical trials,
    • the likelihood of participation
    • prevalence of previously described barriers (ie. transportation, cost)

Qualitative:

  • Identify factors related to clinical trials highlighting patient voices
  • Sample size: 20 patients per site (10 CT participants; 10 non-part)

MD Anderson Department of Lymphoma/Myeloma

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R: Rank score for clinical trials

Birhiray and Birhiray Blood Adv 2023

Drive rank score

Racial or nationality enrollment of the sum of all minority groups relative to the epidemiology of the disease in studies

0 

≤20% of the sum of all minority groups relative to the epidemiology of the disease. 

1 

21%-40%, the sum total of all minority groups relative to the epidemiology of the disease, and at least 1 minority group† reaching 50% relative to the epidemiology of the disease. 

2 

21%-40%, the sum of all minority groups relative to the epidemiology of the disease, and at least 2 minority group† reaching 50% relative to the epidemiology of the disease. 

3 

41%-60%, the sum of all minority groups relative to the epidemiology of the disease, and at least 2 minority groups reaching 60% relative to the epidemiology of the disease. 

4 

61%-80%, the sum of all minority groups relative to the epidemiology of the disease, and at least 3 minority groups reaching 60% relative to the epidemiology of the disease. 

5 

80%, the sum of all minority groups relative to the epidemiology of the disease, and at least 3 minority groups reaching 80% relative to the epidemiology of the disease. 

MD Anderson Department of Lymphoma/Myeloma

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A Call for Action

Food and Drug Omnibus Reform Act (FDORA)

​

Key provisions seek to improve clinical trials by increasing diversity in patient enrollment

MD Anderson Department of Lymphoma/Myeloma

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I: individual strategy

New Strategies for Enhancing Enrollment of Underrepresented Minorites in Lymphoma

Clinical Trials

Nze and Herrera

Blood Advances. 2024

  • Incorporating patient navigators
  • Making communities a part of the research team/process
  • Modernized eligibility criteria
  • Patient Education and resources
  • Provider and research team training
  • Regulatory innovation to reduce burdens.
  • Expanding Clinical Trial Availability
  • Decentralized Clinical Trials (DCTs)
  • Site selection and capacity
  • Geographic consideration
  • Trial selection
  • Universal screening
  • Multidisciplinary Tumor Board Meetings

MD Anderson Department of Lymphoma/Myeloma

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LEO Enrollment Reflects the Demographics of NHL in the US

Cerhan et al, AJH 2024

Residence of LEO participants enrolled 2015-2020 by Rural Urban Code

(n=7735)

MD Anderson Department of Lymphoma/Myeloma

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Study Eligibility

  • Patients with DLBCL or other aggressive B-cell lymphoma
  • Received standard of care anthracycline-based immunochemotherapy
  • Non-missing values for 3 or more of the 5 lab-based criteria

​

@ArushiKhurana4 @MaurerStats

​

White

Black/AA

Hispanic

Other

LEO DLBCL

76%

7%

13%

4%

SEER DLBCL

67%

7%

16%

10%

Who gets left behind in clinical trials of DLBCL?

©2020 Mayo Foundation for Medical Education and Research | slide-14

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LEO Cohort DLBCL�Organ Function Lab Based Ineligibility by Race/Ethnicity

1L DLBCL

Clinical Trial

White

(Non-Hispanic)

Black/AA

(Non-Hispanic)

Hispanic (Any)

Other Minority (Non-Hispanic)

Total

P-Value

(N=1666)

(N=155)

(N=288)

(N=76)

(N=2185)

GOYA, n (%)

269 (16.1%)

39 (25.2%)

47 (16.3%)

17 (22.4%)

372 (17.0%)

0.020

ENGINE, n (%)

409 (24.5%)

57 (36.8%)

82 (28.5%)

23 (30.3%)

571 (26.1%)

0.0052 

POLARIX, n (%)

262 (15.7%)

34 (21.9%)

47 (16.3%)

17 (22.4%)

360 (16.5%)

0.11 

@ArushiKhurana4 @MaurerStats

©2020 Mayo Foundation for Medical Education and Research | slide-15

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Simplifying Eligibility for DLBCL Trials

Harkins et al, Blood Adv 2022

Recommendations for eligibility criteria in 1L DLBCL RCTs using Delphi-method with lymphoma experts from LEO

Disagreement

Essential

Unresolved

Unneccessary

Expert Consensus

Mean (Interquartile range)

MD Anderson Department of Lymphoma/Myeloma

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E: elevate and enhanced training of a diverse research and clinical team

Birhiray and Birhiray Blood Adv 2023

  • Funding mechanisms to established to train diverse investigators and investigators practicing in traditionally underrepresented communities.

​

  • Training should include physicians, advanced providers, nurses, social workers, pharmacists, navigators, medical assistants, students, and other members of the clinical and research team

​

  • Establish diverse study leadership

​

  • Establish diversity among regulatory agencies, journal editors-in-chief, major medical societies studying PIs, and study teams

​

  • Apply FDA regulatory enhancements will certainly promote research diversity

MD Anderson Department of Lymphoma/Myeloma

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  • Created in 2003 to increase participation of underrepresented minorities training in hematology-related fields
  • Expanded to establish continuous pathway including medical students, residents, fellows, junior faculty and PhD scientists
  • 2004-2022: 405 award recipients across 6 different MRI awards

MD Anderson Department of Lymphoma/Myeloma

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2-year program to support career development of early-stage investigators from diverse backgrounds and physicians with demonstrated commitment to increasing diversity in clinical research

Winn Diversity In Clinical Trials Award Program

Cohort 2 2022-2024

Pamela Allen

Eden Biltibo

Ning Dong

Shella Fleur-Lominy

Arushi Khurana

Ricardo Parrondo

Santiago Thibaud

Olatundun Williams

Lena Winestone 

Cohort 3 2023-2025

Muhamad Moustafa

Namrata Chandhok

Hany Elmariah

Keri Maher

Chijioke Nze

Abhay Singh

Senthil Sukumar

​

Cohort 1 2021-2023

Adolfo Enrique Diaz Duque

Annellys Hernandez

Justine Kahn

Luis Malpica Castillo

Sonia Morales

Sarah Noor

Alejandro Sica

Beatriz Wills

  • To develop independent clinical trial investigators engaged in advancing health equity through research and mentoring
    • In-person 5-day intensive workshop on clinical trials design, development, implementation, and community engagement
    • 2-year Community-Oriented Clinical Trialist (COCT) curriculum thorough trfor aining in clinical research design and community engagement methods
    • Individual Professional Development Plan based on a skills assessment and in collaboration with mentor

Manuel Espinoza Gutarra

Supreet Kaur

Busola Oluwole

Oluwatoyosi Onwuemene

Chukwuemeka Uzoka

Austin Wesevich

Yumeng Zhang

MD Anderson Department of Lymphoma/Myeloma

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Leveraging Research to Overcome Lymphoma Disparities

20

Support the research training for members of an underrepresented group

  • W. Brad Jones, PhD Emory (Ga Tech PhD ISyE)

mHealth Approaches for LEO 7/16–5/17

  • Jacob Jordan Emory (U Penn undergraduate)

Pathology Informatics 7/16–5/18

LEO NCI Diversity Supplements: U01 CA195568 �

  • Mazie Tsang, MD Mayo

Investigators Developing Independence 4/24–3/26

(U01 CA195568) Lymphoma Epidemiology of Outcomes Cohort Study Supports Additional Research

U01CA195568 K24CA208132

  • Lauren McCullough, PhD, MPH Emory SPH

Adiposity & lymphoma disparities 7/18–5/20

  • Alexis Romero MD Anderson

Factors influencing participation in clinical research 4/24–3/26

Chijioke Nze MD, MS

Luis Malpica MD

MD Anderson Department of Lymphoma/Myeloma

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LEO PI: Link

LEO

LEO PI: Lossos

LEO PI: Kahl

(ECOG Lead)

LEO PI: Friedberg

(SWOG Lead)

IMPACT PI:

Nowakowski

IMPACT PI:

Cohen

IMPACT PI: Leonard (Alliance Lead)

IMPACT PI:

Flowers

HMC

PCC

EJCH

GMH

AMH

JBACC

NGMC

NYP-Q

NYP-BMH

UTSA

LMC

UT-H-RGV

Mankato

La Crosse

Eau Claire

IMPACT PI:

Siddiqui

IMPACT PI:Smith

Orange County Network Centers

Antelope Valley 

PVH

Denver Health

PCC

Memorial Hospital

LBJ

IMPACT

Optimizing Lymphoma InnoVation in Education & Research (OLIVER)

GOAL:

Expand access to high-quality community-care focused clinical trials to patients with lymphomas served by academic and community health settings particularly supporting access to patients who are rural, economically disadvantaged and/or underrepresented in trials.

(U01 CA195568)

Lymphoma Epidemiology of Outcomes Cohort Study

DHR

MD Anderson Department of Lymphoma/Myeloma