Integrating PET/CT and correlative biomarkers for prospective evaluation of extramedullary disease in relapsed/refractory B-ALL: implications for CAR T-cell therapy.
Authors
Affiliations (12)
Affiliations (12)
- Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.
- Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
- Children's National, Washington, District of Columbia, USA.
- Molecular Imaging Branch, National Cancer Institute, Bethesda, Maryland, USA.
- Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
- Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USA.
- Department of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland, USA.
- Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA.
- Nationwide Children's Hospital, Columbus, Ohio, USA.
- Radiology and Imaging Sciences, National Institutes of Health Clinical Center, Bethesda, Maryland, USA.
- Institute for Cancer and Blood Disorders, Nemours Children's Health, Lisa Dean Moseley Foundation, Wilmington, Delaware, USA.
- Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA [email protected].
Abstract
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. 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. 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. 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. NCT05969002.