A groundbreaking study from Roswell Park Comprehensive Cancer Center has revealed that simple physical performance measures can predict serious complications and survival outcomes in non-Hodgkin Lymphoma (NHL) patients receiving CAR T-cell therapy.
The retrospective cohort study, presented at the 2025 Tandem Meeting, analyzed data from 91 NHL patients treated between 2018 and 2023. The findings demonstrate that basic physical assessments can identify patients at higher risk for developing immune effector cell-associated neurotoxicity syndrome (ICANS) and poor survival outcomes.
Key Risk Factors for ICANS
Patients who experienced recent falls showed a dramatically increased risk of developing ICANS (OR, 5.2; 95% CI, 1.3-20.5; P = .02). Additionally, inability to balance on the left leg for 10 seconds was associated with higher ICANS risk (OR, 2.6; 95% CI, 1.1-6.2; P = .04).
"These 2 measures, together, take less than a minute to implement. They're easy, they're cheap, and we can predict who is going to get neurotoxicity," explained lead researcher Megan Herr, PhD, during the presentation.
Treatment Outcomes and Physical Performance
The study examined patients treated with two CAR T-cell therapies: axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel). Among axi-cel recipients, 59% of patients who developed ICANS couldn't balance on their left leg, compared to 55% of those who didn't develop ICANS. For tisa-cel recipients, these rates were 82% and 29%, respectively.
Survival Implications
Several physical function measures showed significant correlation with reduced overall survival:
- Use of assistive devices (HR, 2.6; P <.01)
- Positive Romberg test (HR, 3.1; P = .02)
- Reduced strength scores (HR, 2.3; P = .01)
Particularly concerning was the finding that patients with elevated CAR-HEMATOTOX scores and at least two adverse physical functions showed a mere 9% one-year overall survival rate.
Patient Population and Response Rates
The study population characteristics included:
- 56% over 60 years old
- 67% male
- 96% with diffuse large B-cell lymphoma
- 72% treatment resistant at cell transfer
- 81% with Karnofsky performance status of 70
Treatment outcomes showed complete responses in 45% of patients, with cytokine release syndrome occurring in 64% and ICANS in 50% of cases. The one-year survival rate across all patients was 57%.
Expert Commentary
Shernan Holtan, MD, chief of Blood and Marrow Transplantation at Roswell Park Comprehensive Cancer Center, emphasized the significance of these findings: "This highlights, that even within a high [CAR-HEMATOTOX group], those patients were at extraordinarily high risk of not benefitting from the CAR T, and these tests are so simple to do. It's going to be interesting to see if others can reproduce this."
