NIMG-11. IDENTIFYING EARLY INDICATORS OF IMMUNOTHERAPEUTIC RESPONSE: CAR T-CELL THERAPY

The current guideline to assess radiological changes in response to immunotherapy, iRANO, faces critical challenges in the determination of progressive disease during the first 6 months from the start of therapy. In patients with recurrent glioblastoma (GBM), immunotherapy induces an inflammatory response that mimics progressive disease, which can lead to premature discontinuation of potentially effective therapy. We investigated the dynamics of tumor growth within the first month of starting immunotherapy with the goal of identifying early indicators that could suggest clinical response. We performed a retrospective review of 8 patients from a Phase 1 Trial of CAR T-Cell therapy that had one MRI scan prior to treatment, during treatment and following treatment. Spherically equivalent radii were extracted from tumor volumes segmented on T1Gd and FLAIR MRIs to quantify the dynamics of tumor growth. Kaplan Meier and Cox Proportional Hazard analysis were performed to the role of tumor dynamics in predicting patient survival. Initial tumor growth velocity during CAR T-cell therapy of >50 mm/year (P=0.0067) was prognostic for overall survival from the time of treatment. An increase in radial T1Gd tumor size of >25% (P=0.046) after receiving two CAR T-Cell cycles also discriminated patient survival from the start of treatment. In addition to the above noted optimal cutoffs, initial T1Gd tumor growth velocity was significant as a continuous variable in cox proportional hazard (HR=0.976, P=0.0404). This significance was retained when controlling for age and sex (HR=0.961, P=0.0429). In this case, more aggressive imageable growth was beneficial to the patient. This increased tumor growth rate may be suggestive of a robust immunological response early in therapy that may be important to anticipate in the clinical management of GBM patients. Increased initial tumor growth velocity during treatments shows promise in identifying patients experiencing clinically relevant response that is predictive of patient survival.