Metabolic PET/CT analysis of aggressive Non-Hodgkin lymphoma prior to Axicabtagene Ciloleucel CAR-T infusion: predictors of progressive disease, survival, and toxicity
Abstract PET/CT is used to evaluate relapsed/refractory non-Hodgkin lymphoma (NHL) prior to chimeric antigen receptor T-cell (CAR-T) infusion at two time points: pre-leukapheresis (pre-leuk) and pre-lymphodepletion chemotherapy (pre-LD). We hypothesized that changes in PET/CT between these time poin...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-08-01
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| Series: | Blood Cancer Journal |
| Online Access: | https://doi.org/10.1038/s41408-023-00895-7 |
| _version_ | 1797578000490823680 |
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| author | William G. Breen Jason R. Young Matthew A. Hathcock Roman O. Kowalchuk Matthew P. Thorpe Radhika Bansal Arushi Khurana N. Nora Bennani Jonas Paludo Jose Villasboas Bisneto Yucai Wang Stephen M. Ansell Jennifer L. Peterson Patrick B. Johnston Scott C. Lester Yi Lin |
| author_facet | William G. Breen Jason R. Young Matthew A. Hathcock Roman O. Kowalchuk Matthew P. Thorpe Radhika Bansal Arushi Khurana N. Nora Bennani Jonas Paludo Jose Villasboas Bisneto Yucai Wang Stephen M. Ansell Jennifer L. Peterson Patrick B. Johnston Scott C. Lester Yi Lin |
| author_sort | William G. Breen |
| collection | DOAJ |
| description | Abstract PET/CT is used to evaluate relapsed/refractory non-Hodgkin lymphoma (NHL) prior to chimeric antigen receptor T-cell (CAR-T) infusion at two time points: pre-leukapheresis (pre-leuk) and pre-lymphodepletion chemotherapy (pre-LD). We hypothesized that changes in PET/CT between these time points predict outcomes after CAR-T. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and other metrics were calculated from pre-leuk and pre-LD PET/CT scans in patients with NHL who received axicabtagene ciloleucel, and assessed for association with outcomes. Sixty-nine patients were analyzed. While single time point PET/CT characteristics were not associated with risk of PD or death, increases from pre-leuk to pre-LD in parenchymal MTV, nodal MTV, TLG of the largest lesion, and total number of lesions were associated with increased risk of death (p < 0.05 for all). LASSO analysis identified increasing extranodal MTV and increasing TLG of the largest lesion as strong predictors of death (AUC 0.74). Greater pre-LD total MTV was associated with higher risk of grade 3+ immune effector cell-associated neurotoxicity syndrome (ICANS) (p = 0.042). Increasing metabolic disease burden during CAR-T manufacturing is associated with increased risk of progression and death. A two variable risk score stratifies prognosis prior to CAR-T infusion and may inform risk-adapted strategies. |
| first_indexed | 2024-03-10T22:16:07Z |
| format | Article |
| id | doaj.art-2216cd6058cc41c898d1c89beb34f7cd |
| institution | Directory Open Access Journal |
| issn | 2044-5385 |
| language | English |
| last_indexed | 2024-03-10T22:16:07Z |
| publishDate | 2023-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Blood Cancer Journal |
| spelling | doaj.art-2216cd6058cc41c898d1c89beb34f7cd2023-11-19T12:25:18ZengNature Publishing GroupBlood Cancer Journal2044-53852023-08-011311510.1038/s41408-023-00895-7Metabolic PET/CT analysis of aggressive Non-Hodgkin lymphoma prior to Axicabtagene Ciloleucel CAR-T infusion: predictors of progressive disease, survival, and toxicityWilliam G. Breen0Jason R. Young1Matthew A. Hathcock2Roman O. Kowalchuk3Matthew P. Thorpe4Radhika Bansal5Arushi Khurana6N. Nora Bennani7Jonas Paludo8Jose Villasboas Bisneto9Yucai Wang10Stephen M. Ansell11Jennifer L. Peterson12Patrick B. Johnston13Scott C. Lester14Yi Lin15Department of Radiation Oncology, Mayo ClinicDepartment of Radiology, Mayo ClinicDepartment of Biomedical Statistics and Informatics, Mayo ClinicDepartment of Radiation Oncology, Mayo ClinicDepartment of Radiology, Mayo ClinicDivision of Hematology, Department of Medicine, Mayo ClinicDivision of Hematology, Department of Medicine, Mayo ClinicDivision of Hematology, Department of Medicine, Mayo ClinicDivision of Hematology, Department of Medicine, Mayo ClinicDivision of Hematology, Department of Medicine, Mayo ClinicDivision of Hematology, Department of Medicine, Mayo ClinicDivision of Hematology, Department of Medicine, Mayo ClinicDepartment of Radiation Oncology, Mayo ClinicDivision of Hematology, Department of Medicine, Mayo ClinicDepartment of Radiation Oncology, Mayo ClinicDivision of Hematology, Department of Medicine, Mayo ClinicAbstract PET/CT is used to evaluate relapsed/refractory non-Hodgkin lymphoma (NHL) prior to chimeric antigen receptor T-cell (CAR-T) infusion at two time points: pre-leukapheresis (pre-leuk) and pre-lymphodepletion chemotherapy (pre-LD). We hypothesized that changes in PET/CT between these time points predict outcomes after CAR-T. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and other metrics were calculated from pre-leuk and pre-LD PET/CT scans in patients with NHL who received axicabtagene ciloleucel, and assessed for association with outcomes. Sixty-nine patients were analyzed. While single time point PET/CT characteristics were not associated with risk of PD or death, increases from pre-leuk to pre-LD in parenchymal MTV, nodal MTV, TLG of the largest lesion, and total number of lesions were associated with increased risk of death (p < 0.05 for all). LASSO analysis identified increasing extranodal MTV and increasing TLG of the largest lesion as strong predictors of death (AUC 0.74). Greater pre-LD total MTV was associated with higher risk of grade 3+ immune effector cell-associated neurotoxicity syndrome (ICANS) (p = 0.042). Increasing metabolic disease burden during CAR-T manufacturing is associated with increased risk of progression and death. A two variable risk score stratifies prognosis prior to CAR-T infusion and may inform risk-adapted strategies.https://doi.org/10.1038/s41408-023-00895-7 |
| spellingShingle | William G. Breen Jason R. Young Matthew A. Hathcock Roman O. Kowalchuk Matthew P. Thorpe Radhika Bansal Arushi Khurana N. Nora Bennani Jonas Paludo Jose Villasboas Bisneto Yucai Wang Stephen M. Ansell Jennifer L. Peterson Patrick B. Johnston Scott C. Lester Yi Lin Metabolic PET/CT analysis of aggressive Non-Hodgkin lymphoma prior to Axicabtagene Ciloleucel CAR-T infusion: predictors of progressive disease, survival, and toxicity Blood Cancer Journal |
| title | Metabolic PET/CT analysis of aggressive Non-Hodgkin lymphoma prior to Axicabtagene Ciloleucel CAR-T infusion: predictors of progressive disease, survival, and toxicity |
| title_full | Metabolic PET/CT analysis of aggressive Non-Hodgkin lymphoma prior to Axicabtagene Ciloleucel CAR-T infusion: predictors of progressive disease, survival, and toxicity |
| title_fullStr | Metabolic PET/CT analysis of aggressive Non-Hodgkin lymphoma prior to Axicabtagene Ciloleucel CAR-T infusion: predictors of progressive disease, survival, and toxicity |
| title_full_unstemmed | Metabolic PET/CT analysis of aggressive Non-Hodgkin lymphoma prior to Axicabtagene Ciloleucel CAR-T infusion: predictors of progressive disease, survival, and toxicity |
| title_short | Metabolic PET/CT analysis of aggressive Non-Hodgkin lymphoma prior to Axicabtagene Ciloleucel CAR-T infusion: predictors of progressive disease, survival, and toxicity |
| title_sort | metabolic pet ct analysis of aggressive non hodgkin lymphoma prior to axicabtagene ciloleucel car t infusion predictors of progressive disease survival and toxicity |
| url | https://doi.org/10.1038/s41408-023-00895-7 |
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