Winkelmann, Michael and Raj, Sandeep S. and Jain, Michael D. and Iacoboni, Gloria and Mueller, Fabian and Hansmann, Leo and Corona, Magdalena and Luna, Alejandro and Jhaveri, Khushali and Shah, Gunjan L. and Scordo, Michael and Mohammad, Turab and Dean, Erin A. and Sheikh, Gabriel T. and Kunz, Wolfgang G. and Tix, Tobias and Buecklein, Veit L. and Bedmutha, Akshay and Leithner, Doris and von Bergwelt-Baildon, Michael and Boardman, Alexander P. and Palomba, M. Lia and Park, Jae H. and Salles, Gilles and Perales, Miguel-Angel and Schoder, Heiko and Subklewe, Marion and Barba, Pere and Locke, Frederick L. and Shouval, Roni and Rejeski, Kai (2025) Optimization and validation of the international metabolic prognostic index for CD19 CAR-T in large B-cell lymphoma. BLOOD CANCER JOURNAL, 15 (1): 144. ISSN 2044-5385,
Full text not available from this repository. (Request a copy)Abstract
While CD19-directed CAR T-cell therapy represents a transformative immunotherapy for relapsed/refractory large B-cell lymphoma (r/r LBCL), more than 50% of patients ultimately progress or relapse. Recently, the International Metabolic Prognostic Index (IMPI) - incorporating age, stage, and metabolic tumor volume (MTV) - was shown to improve prognostication for LBCL frontline treatment. Here, we examine its utility to predict toxicity and survival in CAR-T recipients. This multicenter observational study spanning six international sites included 504 patients with available 18FDG-PET/CT imaging at last response assessment prior to lymphodepletion. Optimal CAR-adapted MTV thresholds were identified in a development cohort (n = 256) and incorporated into a CAR-T-specific IMPI ("CAR-IMPI"). The prognostic performance of CAR-IMPI was validated in an independent cohort (n = 248). CAR-IMPI risk categories, defined by the median (1.35) and terciles (1.07, 1.58), demonstrated significant discrimination for progression-free survival (PFS; p < 0.0001) and overall survival (OS; p < 0.0001) in both cohorts. Multivariate Cox regression confirmed CAR-IMPI as an independent predictor of survival, accounting for pre-lymphodepletion LDH and CRP, performance status, treatment center, and CAR-T product. Patients in the CAR-IMPI high-risk category experienced increased severity of CRS and ICANS, and higher rates of intensive care unit (ICU) admissions. In an exploratory analysis, combining CAR-IMPI with established indices of high-risk systemic inflammation (CAR-HEMATOTOX, InflaMix) further enhanced survival stratification. The CAR-IMPI may provide a potent and validated PET-based tool for risk stratification of clinical outcomes in patients with r/r LBCL receiving CD19 CAR-T therapy. Our data highlight the utility of combining clinical and radiological modalities, with implications for patient selection and the anticipated level-of-care for toxicity management.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LISOCABTAGENE MARALEUCEL; TUMOR BURDEN; OUTCOMES; THERAPY; HODGKIN; IMPACT; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Mar 2026 05:53 |
| Last Modified: | 27 Mar 2026 05:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67969 |
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