CAR T-Cell Therapy Clinical Trials

Brian Hill, MD, PhD: The long-term treatment outcomes for patients treated with CAR T [chimeric antigen-receptor T-cell] therapy are very impressive in the sense that historically we knew that these patients really had very limited overall survival. What we can see in some of the long-term studies is that there are about 30% or 40% of patients who achieve durable remission after treatment with CAR T-cell therapy for relapsed or refractory diffuse large B-cell lymphoma.

This really represents a paradigm shift where previously most of the treatments would have been palliative or clinical trials of new drugs. This really has become the standard of care, and it suggests that patients can be cured with this approach.

Julio Chavez, MD, MS: Given the known adverse effects of CAR T-cell therapy, especially CRS [cytokine response syndrome] and neurotoxicity, there is always a concern of how our older-patient population will tolerate these therapies. The way I see it, it’s more than age. It’s a functional age that is driven by other factors, like physical health or impact of comorbidities.

This interesting study is based on the retrospective study of 77 patients. They include patients over the age of 70 years old, and what they did is they divided patients from 70 to 74 and 75 years and older. Patients received a standard of care CAR T-cell therapy, either tisagenlecleucel or axi-cel. One, the PFS [progression-free survival] was no different, the overall survival was worse in patients older than 75 years old, and more interestingly, it was what they analyzed actually. They did a multivariate analysis that showed the use of axi-cel and risk score, hematopoietic cell therapy comorbidity score that is used commonly in transplant patients. When the score was more than 2, it was associated with a worse PFS. In terms of toxicity, they found out that patients who developed grade 3/4 cytokine release syndrome was associated with higher CIRS [cumulative illness rating scale] score, which is a comorbidity-illness score that measures the comorbidity and the impact on the patients, and also the use of axi-cel was associated with CRS. In addition, the CRES, which is CAR T-cell-related encephalopathy syndrome, was also associated with older age and CRES score of more than 6.

What this tells us is this is a valuable study that is evaluating patients older than 75 years old and the toxicity associated with CAR T-cell therapy. In real life, we do see those adverse effects. We prefer to use the less toxic product that’s proven by this study. We feel the axi-cel, while it’s very effective treating lymphomas, is essentially more toxic than tisagenlecleucel or other similar CAR T cells. However, age by itself is not the only factor that we keep in account. We also take into account other factors, specifically comorbidities, that we call functional age.

Transcript edited for clarity.