Michael Winkelmann, Sandeep S. Raj, Michael D. Jain, Gloria Iacoboni, Fabian Müller, Leo Hansmann, Magdalena Corona, Alejandro Luna, Khushali Jhaveri, Gunjan L. Shah, Michael Scordo, Turab Mohammad, Erin A. Dean, Gabriel T. Sheikh, Wolfgang G. Kunz, Tobias Tix, Veit L. Bücklein, Akshay Bedmutha, Doris Leithner, Michael von Bergwelt-Baildon, Alexander P. Boardman, M. Lia Palomba, Jae H. Park, Gilles Salles, Miguel-Angel Perales, Heiko Schöder, Marion Subklewe, Pere Barba, Frederick L. Locke, Roni Shouval, Kai Rejeski
{"title":"CD19 CAR-T在大b细胞淋巴瘤中的国际代谢预后指标的优化和验证","authors":"Michael Winkelmann, Sandeep S. Raj, Michael D. Jain, Gloria Iacoboni, Fabian Müller, Leo Hansmann, Magdalena Corona, Alejandro Luna, Khushali Jhaveri, Gunjan L. Shah, Michael Scordo, Turab Mohammad, Erin A. Dean, Gabriel T. Sheikh, Wolfgang G. Kunz, Tobias Tix, Veit L. Bücklein, Akshay Bedmutha, Doris Leithner, Michael von Bergwelt-Baildon, Alexander P. Boardman, M. Lia Palomba, Jae H. Park, Gilles Salles, Miguel-Angel Perales, Heiko Schöder, Marion Subklewe, Pere Barba, Frederick L. Locke, Roni Shouval, Kai Rejeski","doi":"10.1038/s41408-025-01338-1","DOIUrl":null,"url":null,"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 <sup>18</sup>FDG-PET/CT imaging at last response assessment prior to lymphodepletion. Optimal CAR-adapted MTV thresholds were identified in a development cohort (<i>n</i> = 256) and incorporated into a CAR-T-specific IMPI (“CAR-IMPI”). The prognostic performance of CAR-IMPI was validated in an independent cohort (<i>n</i> = 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; <i>p</i> < 0.0001) and overall survival (OS; <i>p</i> < 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>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"7 1","pages":""},"PeriodicalIF":11.6000,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Optimization and validation of the international metabolic prognostic index for CD19 CAR-T in large B-cell lymphoma\",\"authors\":\"Michael Winkelmann, Sandeep S. Raj, Michael D. Jain, Gloria Iacoboni, Fabian Müller, Leo Hansmann, Magdalena Corona, Alejandro Luna, Khushali Jhaveri, Gunjan L. Shah, Michael Scordo, Turab Mohammad, Erin A. Dean, Gabriel T. Sheikh, Wolfgang G. Kunz, Tobias Tix, Veit L. Bücklein, Akshay Bedmutha, Doris Leithner, Michael von Bergwelt-Baildon, Alexander P. Boardman, M. Lia Palomba, Jae H. Park, Gilles Salles, Miguel-Angel Perales, Heiko Schöder, Marion Subklewe, Pere Barba, Frederick L. Locke, Roni Shouval, Kai Rejeski\",\"doi\":\"10.1038/s41408-025-01338-1\",\"DOIUrl\":null,\"url\":null,\"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 <sup>18</sup>FDG-PET/CT imaging at last response assessment prior to lymphodepletion. Optimal CAR-adapted MTV thresholds were identified in a development cohort (<i>n</i> = 256) and incorporated into a CAR-T-specific IMPI (“CAR-IMPI”). The prognostic performance of CAR-IMPI was validated in an independent cohort (<i>n</i> = 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; <i>p</i> < 0.0001) and overall survival (OS; <i>p</i> < 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. 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Optimization and validation of the international metabolic prognostic index for CD19 CAR-T in large B-cell lymphoma
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.
期刊介绍:
Blood Cancer Journal is dedicated to publishing high-quality articles related to hematologic malignancies and related disorders. The journal welcomes submissions of original research, reviews, guidelines, and letters that are deemed to have a significant impact in the field. While the journal covers a wide range of topics, it particularly focuses on areas such as:
Preclinical studies of new compounds, especially those that provide mechanistic insights
Clinical trials and observations
Reviews related to new drugs and current management of hematologic malignancies
Novel observations related to new mutations, molecular pathways, and tumor genomics
Blood Cancer Journal offers a forum for expedited publication of novel observations regarding new mutations or altered pathways.