CAR T-Cell Therapy in the Older Person: Indications and Risks

Validated metrics to optimize older adult patient selection for Chimeric Antigen Receptor T-cell therapy (CART) are lacking; however, some preliminary data suggests that geriatric assessments and cumulative illness rating score may be useful tools. In addition, interventions capable of enhancing outcomes in older adults receiving CART have yet to be elucidated. The purpose of this review is to present data extrapolating from other diseases and therapeutic modalities, related to product selection, toxicity mitigation strategies, comprehensive coordinated models of care, and functional optimization of patients.

The most robust data in older adults are among relapsed and refractory (r/r) diffuse large B-cell lymphoma (DLBCL) patients where three products are available with the longest clinical follow up and the most abundant real-world evidence (RWE). Data for the approved CART products for follicular lymphoma (FL) and mantle cell lymphoma (MCL) are relatively new and RWE is lacking in general. Data for CART products in multiple myeloma (MM) and B-cell acute lymphoblastic leukemia (B-ALL) are even more recent, but preliminary data in older adults seem to follow the trend of excellent efficacy in this age group with age-stratified toxicity data limited. Landmark trials and RWE studies indicate that the high response rates of CART for older adult patients, age 65 years and older, are maintained, while toxicity may be amplified. Clinically important toxicities include grade 3 or higher cytokine release syndrome (CRS), neurotoxicity, and infections.