Integrating PET/CT and correlative biomarkers for prospective evaluation of extramedullary disease in relapsed/refractory B-ALL: implications for CAR T-cell therapy
11 affiliations
- 1Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA
- 2Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
- 3Children’s National, Washington, District of Columbia, USA
- 4Molecular Imaging Branch, National Cancer Institute, Bethesda, Maryland, USA
- 5Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA
- 6Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USA
- 7Department of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland, USA
- 8Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA
- 9Nationwide Children’s Hospital, Columbus, Ohio, USA
- 10Radiology and Imaging Sciences, National Institutes of Health Clinical Center, Bethesda, Maryland, USA
- 11Institute for Cancer and Blood Disorders, Nemours Children’s Health, Lisa Dean Moseley Foundation, Wilmington, Delaware, USA
Abstract
Background: Despite advances in immunotherapy for B-cell acute lymphoblastic leukemia (B-ALL), non-central nervous system extramedullary disease (non-CNS EMD) is increasingly recognized. Due to the lack of routine whole-body imaging, the incidence of non-CNS EMD is poorly understood. Fluorodeoxyglucose positron emission tomography/CT (FDG PET/CT) offers a comprehensive approach in detecting EMD involvement, but its utility in B-ALL has not been prospectively evaluated. Furthermore, whether the utilization of cell-free DNA (cfDNA) in B-ALL can improve the identification of EMD is unknown.
Methods: We conducted a prospective, single-center cohort study evaluating FDG PET/CT imaging and correlative molecular biomarkers in patients with relapsed/refractory (R/R) B-ALL undergoing evaluation for chimeric antigen receptor T-cell therapy. Baseline PET/CT was performed prior to infusion, and patients with identified non-CNS EMD underwent post-treatment imaging. Imaging metrics, using artificial intelligence with expert input, included standardized uptake values (SUV). cfDNA was evaluated longitudinally using personalized droplet digital PCR assays and compared with imaging findings and standard disease detection modalities, including flow cytometry, and next-generation sequencing. The primary endpoint was the proportion of non-CNS EMD detected on baseline PET/CT in adults.
Results: Sixteen patients were enrolled; median age was 21.5 years (range, 5–38). Baseline PET/CT identified non-CNS EMD in 44% of patients (5 of 10 (50%) adults and 2 of 6 (33%) children). Non-CNS EMD was multifocal in all affected patients and most commonly involved lymph nodes, kidneys, testes, and soft tissue. Median SUVmax was 17 (range, 13.4–32.3). A prior history of non-CNS EMD was associated with EMD detection on PET/CT at enrollment (p=0.035). In one patient, widespread non-CNS EMD was identified on PET/CT despite negative bone marrow flow cytometry. Peripheral blood cfDNA detected leukemic sequences in 15 of 16 (93.8%) samples with active disease. Peripheral blood cfDNA detected isolated non-CNS EMD in three patients where all other biomarker testing was negative.
Conclusions: Prospective whole-body imaging revealed a high prevalence of multifocal non-CNS EMD. Integration of whole-body imaging with cfDNA may enable more comprehensive disease evaluation in patients with R/R B-ALL. Larger prospective studies are needed to define the true incidence and clinical significance of non-CNS EMD.
Trial registration number: NCT05969002.
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BibTeX
@article{solter2026integrating,
title = {{Integrating PET/CT and correlative biomarkers for prospective evaluation of extramedullary disease in relapsed/refractory B-ALL: implications for CAR T-cell therapy}},
author = {Mark L. Solter and Yannan J Wang and Grace Li and Fahmida Haque and Brynn B Duncan and Xiaolin Wu and Stephanie Harmon and Bonnie Yates and Dana Delgado Colon and Hao-Wei Wang and Constance M Yuan and Nisha Patel and Victoria M Giordani and Chloe M Sachs and Chloe N Hoang and John C Molina and Alexander W Rankin and Toni Foley and Casey Mcgrath and Flavia Gava and Chelsea Lamplugh and Alexandra Dreyzin and Sara K Silbert and Ismail Baris Turkbey and Esther Mena and Evrim B Turkbey and R Taylor Sundby and Nirali N Shah},
journal = {Journal for Immunotherapy of Cancer},
year = {2026},
month = nov,
doi = {10.1136/jitc-2026-016031},
url = {https://doi.org/10.1136/jitc-2026-016031},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Integrating PET/CT and correlative biomarkers for prospective evaluation of extramedullary disease in relapsed/refractory B-ALL: implications for CAR T-cell therapy
AU - Mark L. Solter
AU - Yannan J Wang
AU - Grace Li
AU - Fahmida Haque
AU - Brynn B Duncan
AU - Xiaolin Wu
AU - Stephanie Harmon
AU - Bonnie Yates
AU - Dana Delgado Colon
AU - Hao-Wei Wang
AU - Constance M Yuan
AU - Nisha Patel
AU - Victoria M Giordani
AU - Chloe M Sachs
AU - Chloe N Hoang
AU - John C Molina
AU - Alexander W Rankin
AU - Toni Foley
AU - Casey Mcgrath
AU - Flavia Gava
AU - Chelsea Lamplugh
AU - Alexandra Dreyzin
AU - Sara K Silbert
AU - Ismail Baris Turkbey
AU - Esther Mena
AU - Evrim B Turkbey
AU - R Taylor Sundby
AU - Nirali N Shah
PY - 2026
DA - 2026/11/03
JO - Journal for Immunotherapy of Cancer
DO - 10.1136/jitc-2026-016031
UR - https://doi.org/10.1136/jitc-2026-016031
AB - Background: Despite advances in immunotherapy for B-cell acute lymphoblastic leukemia (B-ALL), non-central nervous system extramedullary disease (non-CNS EMD) is increasingly recognized. Due to the lack of routine whole-body imaging, the incidence of non-CNS EMD is poorly understood. Fluorodeoxyglucose positron emission tomography/CT (FDG PET/CT) offers a comprehensive approach in detecting EMD involvement, but its utility in B-ALL has not been prospectively evaluated. Furthermore, whether the utilization of cell-free DNA (cfDNA) in B-ALL can improve the identification of EMD is unknown. Methods: We conducted a prospective, single-center cohort study evaluating FDG PET/CT imaging and correlative molecular biomarkers in patients with relapsed/refractory (R/R) B-ALL undergoing evaluation for chimeric antigen receptor T-cell therapy. Baseline PET/CT was performed prior to infusion, and patients with identified non-CNS EMD underwent post-treatment imaging. Imaging metrics, using artificial intelligence with expert input, included standardized uptake values (SUV). cfDNA was evaluated longitudinally using personalized droplet digital PCR assays and compared with imaging findings and standard disease detection modalities, including flow cytometry, and next-generation sequencing. The primary endpoint was the proportion of non-CNS EMD detected on baseline PET/CT in adults. Results: Sixteen patients were enrolled; median age was 21.5 years (range, 5–38). Baseline PET/CT identified non-CNS EMD in 44% of patients (5 of 10 (50%) adults and 2 of 6 (33%) children). Non-CNS EMD was multifocal in all affected patients and most commonly involved lymph nodes, kidneys, testes, and soft tissue. Median SUVmax was 17 (range, 13.4–32.3). A prior history of non-CNS EMD was associated with EMD detection on PET/CT at enrollment (p=0.035). In one patient, widespread non-CNS EMD was identified on PET/CT despite negative bone marrow flow cytometry. Peripheral blood cfDNA detected leukemic sequences in 15 of 16 (93.8%) samples with active disease. Peripheral blood cfDNA detected isolated non-CNS EMD in three patients where all other biomarker testing was negative. Conclusions: Prospective whole-body imaging revealed a high prevalence of multifocal non-CNS EMD. Integration of whole-body imaging with cfDNA may enable more comprehensive disease evaluation in patients with R/R B-ALL. Larger prospective studies are needed to define the true incidence and clinical significance of non-CNS EMD. Trial registration number: NCT05969002.
SN - 2051-1426
ER -