CONTRALATERAL TRANSIENT CONTRAST ENHANCEMENT IN A PATIENT WITH IDH1WT MGMT PROMOTER-METHYLATED GBM RESPONDING TO TMZ AND INDIVIDUALIZED MULTIMODAL IMMUNOTHERAPY

Abstract Immunotherapy-induced MRI changes remain challenging when treating GBM patients with immunotherapy as part of a combined treatment. The iRANO criteria provide a decision-tree in order to avoid over- and under-treatment reactions when contrast-enhancing lesions become visible and should be interpreted. We report a 34-year female, 34 weeks pregnant, who presented with epilepsy, and was diagnosed with IDH1wt MGMT promoter-methylated GBM after biopsy. On MRI, the left occipital lesion was mostly cystic-necrotic with peripheral contrast enhancement, and crossed over the corpus callosum to the right. The volume was calculated as 64 cm³ (abc/2 formula). She was treated with radiochemotherapy and 12 TMZm cycles. Within each TMZ cycle 5 days of immunogenic cell death (ICD) therapy (5 injections with Newcastle Disease Virus and 5 sessions of modulated electrohyperthermia (Oncotherm 50 min 40-60 Watt) was added at days 8 to 12. After all chemo-/ICD-therapy we continued with active specific immunotherapy: two autologous mature monocyte-derived dendritic cell vaccines loaded with ICD therapy-induced serum-derived antigenic extracellular microvesicles and apoptotic bodies (IO-Vac®). One month after the second IO-Vac®, 17 months after diagnosis, a temporal right FLAIR-visible region showed expansion, and three months later also diffuse contrast enhancement, which was confirmed in a control scan one month later. The original tumor was meanwhile reduced to 16 cm³. However, in the last available scan, two months after the former, the contrast enhancement was disappeared, and the pathologic area on FLAIR was diminished. The original tumor size was reduced to 2 cm³, two year after first diagnosis. She showed allergic skin reactions to TMZ, which was covered with systemic histamine intake. There were no side effects related to multimodal immunotherapy. Transient MRI changes can be observed even in distance from the original tumor and can be interpreted as immune-mediated effects when the original tumor is responding.