Immu-05. cd8 immunopet imaging is able to monitor the immune response sensitively and specifically in gbm patients following neoadjuvant checkpoint blockade immunotherapy

Abstract The sensitive and specific evaluation of treatment response in glioblastoma (GBM) patients following immunotherapy is a clinical dilemma. Traditional MRI assessments to visualize and quantify intracranial tumor burden following immunotherapy cannot reliably differentiate tumor progression and pseudo progression remains a complicating factor. In this study, we provide an early report on the use of an investigational new functional imaging PET tracer (CD8 ImmunoPET, 89Zr-crefmirlimab berdoxam, ImaginAb) prior to and immediately following neoadjuvant checkpoint blockade immunotherapy in five patients with recurrent GBM. Tumor samples were collected from each patient at surgery following a two-week neoadjuvant checkpoint blockade to assess gene expression changes and TIL density. We then evaluated how such tumor measurements correlated with PET metrics obtained at baseline and within 2 weeks after treatment initiation which included standardized uptake values (SUVmax, SUVpeak, and SUVmean), and two proposed new metrics indicating the Volume of Immunometabolism (VIM), and the Total Lesion or Lymph nodes’ T cells called TLTc (TLTc = VI x SUVmean) in the tumor bed and lymph node basins (neck, axillae, and inguinal regions). CD8 ImmunoPET demonstrated tracer uptake in the intracranial tumor at both time points, as well as specific physiologic uptake in lymph node basins, spleen, liver, and bone marrow. Neoadjuvant checkpoint blockade with PD-1 +/- CTLA-4 mAb (Nivolumab, Ipilimumab, BMS) at 2 weeks induced variable changes in SUV, but in four of the five initial patients studied in this clinical trial, an increase in VI and TLTc was observed within the tumor bed. Tracer uptake was associated with elevated T cell infiltration into the tumor bed and gene expression changes indicative of interferon signaling and immune cells in these same patients. Our early findings identify a noninvasive functional imaging platform to evaluate the immunometabolism secondary to T cell infiltration and/or activation changes following immunotherapy in GBM patients.