Addressing the Unique Challenges of Cell Therapies for Pediatric & Geriatric Patients

Tailoring Cell Therapies for Pediatric and Elderly Patients: Addressing Unique Safety Challenges and Efficacy Needs

Oksana Fabri, MD, PhD, CMD (Senior Medical Director, Therapeutic Area Medical Lead at Allucent)

Recent advancements in cell and gene therapies (CGT) have introduced promising treatment options for a wide range of conditions across all age groups. However, it has become increasingly evident that distinct therapeutic strategies are necessary for specific patient populations, particularly pediatric and geriatric groups, due to their unique physiological and clinical needs.

As we move toward broader clinical applications, it is essential to recognize that not all patient populations will respond to these therapies in the same way. Pediatric and elderly patients, in particular, present unique physiological and immunological factors that can significantly impact the safety and efficacy of cell-based treatments. These two groups differ significantly from the general adult population in aspects such as immune function, metabolic rate, and response to medications, presenting unique challenges for the application of cell therapies. These differences necessitate careful adjustments in dosing, vigilant monitoring, and comprehensive long-term follow-up to ensure safety and maximize therapeutic outcomes.

Pediatric Considerations: Ensuring Safety in a Rapidly Developing Organism

Physiological and Immunological Differences in Children

Pediatric patients, particularly infants and young children, possess rapidly developing physiological systems that respond uniquely to therapeutic interventions. Their immune responses tend to be stronger and more active compared to adults, which can increase the likelihood of intensified reactions to cell therapies, including a heightened risk for cytokine release syndrome (CRS).

The distinct stages of growth and immune maturation from infancy through adolescence significantly impact pharmacokinetics, immune tolerance, and overall therapeutic outcomes. These age-specific physiological variations underscore the critical need for tailored treatment strategies that address the unique developmental and immunological profiles within this population.

Dose Optimization and Safety Protocols in Pediatric Cell Therapy

The smaller body size and unique metabolic rates in children necessitate that dosing should be calculated with precision, often differing substantially from adult dosing standards. Overestimating the dose can elevate the risk of toxicity, while underestimating may compromise therapeutic efficacy. As a result, pediatric clinical trials frequently utilize weight-based or body-surface-area dosing models to achieve precise, individualized treatment.

Beyond dose adjustments, pediatric cell therapy requires rigorous and specialized safety protocols. Continuous monitoring for early signs of adverse reactions is essential, as pediatric patients may experience rapid disease progression and more immediate therapeutic responses. This specialized oversight ensures that any adverse effects are identified and managed promptly to maintain optimal safety and efficacy.

Long-Term Follow-Up in Pediatric Cell Therapy

A distinctive requirement of cell therapy in pediatric populations is the need for long-term follow-up. Due to their young age at the time of treatment, pediatric patients may live for decades post-therapy, and the enduring effects of cell-based interventions remain an area under active investigation.

This extended follow-up requirement presents unique logistical and ethical challenges, necessitating comprehensive frameworks for continuous tracking and support throughout the patient’s life. To address these complexities, clinical trials in pediatric cell therapy increasingly incorporate long-term monitoring protocols that extend into young adulthood and, in some cases, beyond. These protocols include regular evaluations such as routine health assessments, immune function monitoring, and vigilance for potential late-onset adverse effects. This structured approach supports proactive health management and contributes to the ongoing understanding of long-term outcomes in pediatric cell therapy recipients.

Elderly Populations: Adapting Cell Therapies for an Aging Organism

In older patients, age-related physiological changes play a crucial role in the administration and efficacy of cell therapies.

Physiological Changes in Elderly Patients

Aging is accompanied by a natural decline in immune system function (immunosenescence), which can impact the effectiveness of cell therapies, particularly those relying on a robust immune response. Additionally, older patients may have multiple comorbidities that complicate cell therapy administration and amplify the risk of adverse effects.

Dose Adjustments and Monitoring Requirements

For older patients, dosing strategies must account for diminished organ function, including renal and hepatic function, which can affect drug metabolism and clearance rates. Clinical trials involving elderly patients frequently use adjusted dosing algorithms that consider these age-related physiological factors to minimize risks while optimizing therapeutic efficacy.

Monitoring requirements are also heightened in geriatric patients

Given the increased likelihood of pre-existing conditions and the general vulnerability associated with aging, comprehensive monitoring protocols are crucial, including routine blood work, cardiovascular assessments, and imaging studies. The establishment of geriatric care teams within clinical trials is becoming a best practice to promptly identify any adverse effects or complications arising from cell therapy and ensure geriatric-specific needs are met.

Long-Term Follow-Up and Quality of Life in Geriatric Cell Therapy

While pediatric patients require decades of post-therapy monitoring, older adults present a different set of long-term considerations. For geriatric patients, the primary therapeutic goals often encompass not only disease control or remission but also the enhancement of quality of life and the preservation of independence. Increasingly, clinical trials for elderly patients are incorporating quality-of-life assessments and functional evaluations to ensure that novel therapies do not inadvertently compromise physical or cognitive well-being.

Addressing Safety and Efficacy Challenges in Clinical Trials

Adaptive Trial Designs

To address the diverse needs of pediatric and elderly populations, many clinical trials now incorporate adaptive trial designs. These flexible trial designs allow for modifications based on interim results, enabling adjustments in dosing, monitoring, and follow-up protocols as more data is gathered. For example, early trial phases may include close examination of age-related responses, allowing researchers to fine-tune interventions for specific age groups in later phases.

Enhanced Monitoring Protocols

Enhanced monitoring protocols have also become standard in trials involving these special populations. Pediatric trials may involve more frequent and detailed imaging and blood tests to capture early signs of treatment response or adverse effects. For geriatric patients, clinical trials often incorporate cardiology, nephrology, and general geriatric consultations to address age-related vulnerabilities.

Focused Outcome Measures

Clinical trials for cell therapies are increasingly incorporating outcome measures tailored to pediatric and geriatric populations. For pediatric patients, this might mean tracking developmental milestones and growth patterns. For geriatric patients, functional status and quality-of-life assessments are commonly included. By establishing these specific outcome measures, researchers can gather data that directly reflects the therapeutic value and safety of cell therapies in each age group.

Conclusion

As cell therapy continues to evolve, the need for tailored approaches to pediatric and elderly populations has become increasingly clear. Addressing the unique physiological and safety challenges of these groups is essential to extending the benefits of cell therapies to broader, more diverse patient populations.

The implementation of adaptive trial designs, age-specific dosing strategies, and rigorous monitoring and follow-up protocols ensure safe and effective application of innovative treatments in cell and gene therapy across all age groups. Prioritizing safety, efficacy, and quality of life establishes a foundation for a new era of personalized multigenerational cell therapy solutions to improve patient outcomes and broaden therapeutic access.

Contact us to learn more about Allucent’s expertise in the challenges of pediatric and geriatric cell and gene therapies.

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