Optimization and validation of the international metabolic prognostic index for CD19 CAR-T in large B-cell lymphoma

Winkelmann M, Raj SS, Jain MD, Iacoboni G, Müller F, Hansmann L, Corona M, Luna A, Jhaveri K, Shah GL, Scordo M, Mohammad T, Dean EA, Sheikh GT, Kunz WG, Tix T, Bücklein VL, Bedmutha A, Leithner D, von Bergwelt-Baildon M, Boardman AP, Palomba ML, Park JH, Salles G, Perales MA, Schöder H, Subklewe M, Barba P, Locke FL, Shouval R, Rejeski K (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Blood Cancer Journal Nature Publishing Group / Nature Publishing Group: Open Access Journals - Option B

Book Volume: 15

Article Number: 144

Journal Issue: 1

DOI: 10.1038/s41408-025-01338-1

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.

Involved external institutions

Memorial Sloan Kettering Cancer Center US United States (USA) (US) Klinikum der Universität München (LMU Klinikum) DE Germany (DE) H. Lee Moffitt Cancer Center & Research Institute US United States (USA) (US) Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron ES Spain (ES) Bayerisches Zentrum für Krebsforschung (BZKF) DE Germany (DE) Universitätsklinikum Regensburg DE Germany (DE) Indiana University Indianapolis (IUI) US United States (USA) (US) University of Florida US United States (USA) (US) Deutsches Konsortium für Translationale Krebsforschung (DKTK) DE Germany (DE) Weill Cornell Medicine US United States (USA) (US)

How to cite

APA:

Winkelmann, M., Raj, S.S., Jain, M.D., Iacoboni, G., Müller, F., Hansmann, L.,... Rejeski, K. (2025). Optimization and validation of the international metabolic prognostic index for CD19 CAR-T in large B-cell lymphoma. Blood Cancer Journal, 15(1). https://doi.org/10.1038/s41408-025-01338-1

MLA:

Winkelmann, Michael, et al. "Optimization and validation of the international metabolic prognostic index for CD19 CAR-T in large B-cell lymphoma." Blood Cancer Journal 15.1 (2025).

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