Clinical Frailty Scores Predict Survival After CAR-T Therapy for B-Cell Lymphoma 

Clinical Frailty Scale scores predict overall survival (OS) among adult patients undergoing chimeric antigen receptor T-cell (CAR T) therapy for relapsed and refractory B-cell lymphoma, according to a single-center cohort study presented in a poster session at the ASH Annual Meeting 2023.

“Conducting serial frailty assessments in patients undergoing CAR-T therapy is feasible,” reported Anca Prica, MD, of the Princess Margaret Cancer Centre in Toronto, Canada, and coauthors. “Overall, patients appear to be impaired at baseline, worsen through the first 1 to 3 months, and improve by 12 months if in remission.”

The study authors examined whether frailty assessments before CAR-T therapy for lymphoma predicts acute toxicities (organ toxicity, intensive care unit [ICU] admission, prolonged hospitalization, readmission), and OS. They also evaluated patients’ changes in frailty over time, and whether changes in frailty before and after CAR-T treatment correlated with OS. Previous research found that fit, less-frail patients had better CAR-T response, progression-free survival (PFS), and OS rates, compared with frail patients.

Laboratory blood tests and frailty assessments were taken at baseline, and then frailty was assessed at 1 month, 3 months, 6 months, and 12 months after CAR-T infusion, using a variety of assessment instruments and scales, including the Clinical Frailty Scale (CFS), Grip Strength and Gait Speed, PHQ (Patient Health Questionnaire) 2/9, and ESAS, Mini-Cog, FACT-Cog, EORTC QLQ-C30, and neuropsychology battery. At baseline, additional assessments included the Vulnerable Elders Survey (VES-13), Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) and Cumulative Illness Rating Scale (CIRS).

The study cohort included 52 patients, aged 22 to 81 years, with non-Hodgkin lymphoma diagnoses; 54% were male. Half had diffuse large B-cell lymphoma (DLBCL) and 7 (14%) had high grade B cell lymphoma. Three (6%) patients each had follicular lymphoma and primary mediastinal B cell lymphoma. Most (65%) patients had ECOG performance status scores of 0 or 1. Most (43; 83%) patients were treated with axicabtagene ciloleucel, and 6 (12%) received tisagenlecleucel. Three (6%) were listed by the study authors as receiving JCAR Trial CAR-T.

At a median follow-up of 3.8 months, OS correlated with baseline ECOG score (P =.02), LDH (P <.001), CRP (P =.02), VES-13 score (P =.004), and CFS score (P =.04). Cases of immune effector cell-associated neurotoxicity syndrome (ICANS) or patient deaths were too few in number to analyze the association between ICANS and OS.

Frailty measures did not predict cytokine release syndrome (CRS) severity but most patients in the cohort had low-grade CRS, thanks to proactive management, the coauthors noted. 

In a multivariate Cox regression analysis, only CFS score predicted OS (P =.021). CFS was the only repeated frailty measure the authors found to have clinically significant changes over time, “suggesting an element of reversible functional impairment related to patients’ lymphoma.”

“Enrollment is ongoing and data on [a] larger number of patients with longer term follow-up is needed,” the authors wrote. 

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Prica A, Coley T, Aitken R, et al. Frailty impact on outcomes of patients undergoing chimeric antigen receptor T-cell (CAR T) therapy at Princess Margaret Cancer Centre: a prospective pilot study. Presented at ASH 2023. December 9-12, 2023. San Diego, CA. Abstract 3768.