Patients undergoing chimeric antigen receptor t-cell (CAR-T) therapy face unique toxicities and hospitalization outcomes that vary significantly in incidence and severity. Evaluating biomarkers of frailty may help identify patients at risk for adverse outcomes and allow for enhanced care planning. We hypothesized that frailty assessments measured at the time of CAR T-cell therapy would identify patients at increased risk for toxicities, prolonged hospitalizations, higher use of ancillary services such as PT/OT, and worse overall outcomes.

We performed a retrospective study of frailty syndromes and outcomes post CAR-T therapy for patients with lymphoma at the University of Nebraska Medical Center. We included 143 patients with diffuse large B-cell lymphoma (DLBCL) or high-grade lymphoma that underwent CAR-T therapy between 2018-2024. The median age of the patient population was 64 (range 24-84) years, 64% of the patients were male, and all patients had a commercial indication for CAR-T therapy. Among the 143 patients, 100 received liso-cel and 43 received axi-cel therapy.

We evaluated the prevalence of frailty syndromes by utilizing ECOG performance status, malnutrition status, Charlson comorbidity index, polypharmacy, and Glasgow Prognosis Scale. The Glasgow Prognosis Score (GPS) is a clinically validated prognostic tool using markers of systemic inflammation (CRP) and nutritional status (albumin) to generate scores ranging from 0 (best prognosis) to 2 (worst prognosis). Prior to CAR T-cell infusion 104 (72%) patients had a GPS 0, 31 (22%) had a GPS 1, and 8 (6%) had a GPS of 2. Forty-five (31%) patients had a diagnosis of malnutrition, 110 (80%) patients had an ECOG score of ≥1, and 87 (61%) patients met a definition of polypharmacy with five or more chronic medications.

We next evaluated an association between frailty biomarkers and adverse events. A GPS score of 1-2 vs. 0 was associated with an increased risk of grade 1-4 immune effector cell associated neurotoxicity syndrome (ICANS) (66 % vs 30%, p < 0.001) and grade 1-4 cytokine release syndrome (85% vs 57%, p = 0.0025). Age and CAR-T product were not for significantly associated with neurotoxicity (p = 0.9 and p = 0.06). A multivariate analysis (MVA) of neurotoxicity was performed including age, GPS, ECOG, and CAR-T product with only GPS resulting as significant (odds ratio (OR) 5.1, p = <0.001).

Higher GPS was associated with increased utilization of supportive care resources, where GPS 1-2 vs 0 featured increased physical therapy referrals (77% vs 37%, p < 0.001) and nutrition consultation (79% vs 45%, p = 0.0002). Twenty-eight (62%) patients diagnosed with malnutrition were evaluated by PT/OT compared to 40 patients (41%) without a malnutrition diagnosis (p = 0.017).

We evaluated factors predictive of length of stay and discharge location. GPS, polypharmacy, malnutrition diagnosis, and ECOG performance status were associated with increased length of stay. Patients with a GPS of 0 vs 1-2 were hospitalized for a median of 11 days vs 16 (p < 0.001). Higher GPS score was associated with increased risk of discharge to acute rehab or long term acute care with 23% of patients with a GPS score of ≥1 requiring rehab compared to 5% of patients with a GPS of 0 (p = 0.003). A MVA was performed for discharge to rehab including age, GPS, poly-pharmacy, and CAR-T product with GPS remaining significantly associated with discharge to rehab (OR 5.5, p = 0.003).

We assessed the correlation between frailty markers and survival outcomes. GPS, poly-pharmacy, malnutrition, and ECOG performance scale were significantly associated with overall survival (OS). The median OS for patients with a GPS of 0 vs 1-2 was 33 months vs 10 (p < 0.001). Patients that had a diagnosis of malnutrition vs without had a median OS of 8.7 months vs 33 (p < 0.001). Poly-pharmacy was negatively associated with OS (19 vs 47 months, p = 0.02). A MVA including age, GPS, poly-pharmacy, ECOG, and malnutrition was performed with GPS and malnutrition remaining significantly associated with OS (hazard ratio (HR) 2.65 and p = 0.0001, HR 2.6 and p = 0.0002).

Our findings highlight the clinical impact frailty markers have on identifying patients with increased care needs and higher risk of poor outcomes. These data support efforts to study early intervention strategies to improve physical de-conditioning and malnutrition for patients with lymphoma undergoing CAR T-cell therapy.

This content is only available as a PDF.
2025
Sign in via your Institution