Are Mandatory Diversity Plans Working for Adoptive Cell Therapies?

Diversity plan mandates are increasingly becoming critical success factors in adoptive cell therapy (ACT) trials and the future of personalized medicine in immunology and oncology. 

Adoptive cell therapy (ACT) represents a promising frontier in oncology, offering innovative treatments for various cancers. However, to ensure these therapies are effective, safe, and applied across diverse populations, it is crucial to maximize diversity, patient access and enrollment in clinical trial. 

Diversity in clinical trials is not just a regulatory requirement but a scientific necessity. Clinical trials must include participants from diverse backgrounds to ensure that therapies are effective for all populations, particularly for conditions like multiple myeloma, which disproportionately affects Black men and women.² Regulatory bodies, especially in Phase 3 trials, mandate the inclusion of diverse populations to enhance the generalizability of trial results​​. 

The Importance of Mandatory Diversity Plans in Adoptive Cell Therapy Trials 

A diversity plan becomes mandatory in Phase 3 clinical trials to ensure that the treatments being tested are applicable and effective across all segments of the population. However, implementing diversity plans for ACT trials before Phase 3 is critical as they present unique challenges.  

For example, ACT studies are most often conducted in large academic centers which limit participant access. They are high patient burden studies requiring multiple infusions and autologous collection in an in-patient setting and therefore a potential for hesitancy due to therapy complexity in the small patient populations that qualify for the studies.³ Implementing a diversity plan in ACT trials can help mitigate some of these challenges, with impacts including:  

• Better Understanding of Treatment Effects: Diverse representation helps to identify the efficacy and safety in patient populations who will benefit from the treatments.⁴ This is crucial for ACT, which often involves personalized approaches and can have different effects and toxicities based on genetic, biological, and socio-economic factors. 
• Regulatory Compliance: Regulatory bodies such as the FDA and EMA have stringent guidelines that require diversity in clinical trials.⁵ Compliance with these regulations is mandatory for the approval of new therapies, ensuring that they are safe and effective for the broader population.
• Addressing Health Disparities: Mandatory diversity plans help to address existing health disparities by including underrepresented groups in clinical research. For example, multiple myeloma has a higher prevalence in Black men and women, making it essential to include them in trials to develop effective treatments for this population. 
• Robust Data Collection: Phase 3 trials are the final step before a therapy can be approved for public use. Including diverse populations ensures that the data collected is comprehensive and reflects the potential real-world application of the therapy. 

Insights from Regulatory Trends and Patient Experiences 

Recent regulations emphasize the importance of diversity in clinical trials. For instance, in Europe, initiatives like ATMP Engage focus on securing access to cell therapies for disadvantaged groups, ensuring that drug development occurs in the right patient setting​​. 

Patient insights reveal that the decision to participate in clinical trials is influenced by various factors, including previous experiences with similar therapies, the perceived complexity of the trial, and the travel required to reach trial sites.⁷ For example, many patients found the concept of adoptive cell therapy intimidating due to previous experiences with intensive treatments like stem cell therapy​.  

Strategies to Enhance Diversity and Enrollment for ACT 

Several strategies to maximizing diversity, patient access and enrollment in adoptive cell therapy clinical trials can be utilized to develop therapies that are safe and effective for all patients, including: 

• Expanding Trial Sites: Conducting trials at a variety of locations, including community hospitals and clinics in underserved areas, can increase access. The use of telemedicine in decentralized trials also broadens the reach. 
• Financial Support: Offering financial assistance for travel, accommodation, and other expenses can alleviate the economic burden on patients, encouraging participation.
• Community Engagement: Building trust within communities through partnerships with local organizations, community leaders, and patient advocacy groups can enhance participation. Culturally tailored communication and education initiatives are vital.
• Raising Awareness: Targeted campaigns, social media, and healthcare providers can inform potential participants about available trials. Simplifying the enrollment process and providing clear, accessible information can also help. 
• Inclusive Eligibility Criteria: Designing trials with broad eligibility criteria ensures a wider range of patients can participate. Excluding populations, such as those with co-morbidities, limits the diversity of the study population.
• Patient-Centric Approaches: Involving patients in the design and implementation of trials ensures their needs and preferences are considered. This includes flexible scheduling, home visits for data collection, and continuous feedback mechanisms.

The mandatory diversity plans in Phase 3 ACT trials underscore the commitment to health equity and the development of robust, generalizable data for new cancer therapies.

The mandatory diversity plans in Phase 3 ACT trials underscore the commitment to health equity and the development of robust, generalizable data for new cancer therapies. However, by addressing barriers to participation and implementing inclusive strategies throughout the drug development process from early-phase to commercialization, especially in high patient-burden trials such as ACT studies, the medical community can ensure the success and broad applicability of life-saving advancements.  

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Contributors 

Jane Bentley, PhD | Vice President, Therapeutic Strategy and Innovation in Oncology  

Abhi Gupta | Senior Vice President & Head of Cell & Gene Therapy 

Chris Keuker, MD | Executive Medical Director in Medical Management  

James Barwick-Silk, PhD | Senior Director, Strategy in Cell & Gene Therapy 

References 

1. Odstrcil MS, Lee CJ, Sobieski C, Weisdorf D, Couriel D. Access to CAR T-cell therapy: Focus on diversity, equity and inclusion. Blood Rev. 2024;63:101136. doi:10.1016/j.blre.2023.101136. 
2. Schwartz AL, Alsan M, Morris AA, Halpern SD. Why diverse clinical trial participation matters. New England Journal of Medicine. 2023;388(14):1252-1254. doi:10.1056/nejmp2215609  
3. Ahmed N, Shahzad M, Shippey E, et al. Socioeconomic and Racial Disparity in Chimeric Antigen Receptor T Cell Therapy Access. Transplant Cell Ther. 2022;28(7):358-364. doi:10.1016/j.jtct.2022.04.008. 
4. Faruqi AJ, Ligon JA, Borgman P, et al. The impact of race, ethnicity, and obesity on CAR T-cell therapy outcomes. Blood Adv. 2022;6(23):6040-6050. doi:10.1182/bloodadvances.2022007676 
5. Salib V. Regulating and authorizing medicines: A comparison of the FDA and EMA. Pharma News Intelligence. March 24, 2023.  
6. Munshi NC. Multiple myeloma presents added burden for African Americans: Dana Farber Cancer Institute Insights. September 20, 2021.  
7. McDonough K, Ouelette M, Gillespie S, Prock J. Embedding the patient voice in decentralized clinical trials. Syneos Health Insights Hub. June 9, 2023.