Optimization and validation of the international metabolic prognostic index for CD19 CAR-T in large B-cell lymphoma Journal Article
| Authors: | Winkelmann, M.; Raj, S. S.; Jain, M. D.; Iacoboni, G.; Müller, F.; Hansmann, L.; Corona, M.; Luna, A.; Jhaveri, K.; Shah, G. L.; Scordo, M.; Mohammad, T.; Dean, E. A.; Sheikh, G. T.; Kunz, W. G.; Tix, T.; Bücklein, V. L.; Bedmutha, A.; Leithner, D.; von Bergwelt-Baildon, M.; Boardman, A. P.; Palomba, M. L.; Park, J. H.; Salles, G.; Perales, M. A.; Schoder, H.; Subklewe, M.; Barba, P.; Locke, F. L.; Shouval, R.; Rejeski, K. |
| Article Title: | Optimization and validation of the international metabolic prognostic index for CD19 CAR-T in large B-cell lymphoma |
| Abstract: | <p>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.</p> |
| Keywords: | tumor burden; outcomes; therapy; impact; hodgkin; lisocabtagene maraleucel |
| Journal Title: | Blood Cancer Journal |
| Volume: | 15 |
| Issue: | 1 |
| ISSN: | 2044-5385 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2025-08-26 |
| Language: | English |
| ACCESSION: | WOS:001559434000001 |
| DOI: | 10.1038/s41408-025-01338-1 |
| PROVIDER: | wos |
| Notes: | Article -- 144 -- Source: Wos |
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