18FDG PET/CT Parameters for the Prediction of CAR T-Cell Therapy Response among Patients with Large B-Cell Lymphoma

Abstract

<h3>Purpose/Objective(s)</h3> To define the prognostic value of quantitative positron emission tomography/computed tomography (PET/CT) parameters in diffuse large B-cell lymphoma (DLBCL) patients undergoing CAR T-cell therapy. <h3>Materials/Methods</h3> Sixty-three patients who had PET-CT scans done pre-CAR T infusion were retrospectively identified and analyzed in a single institution database of DLBCL patients treated with commercially available CD19-targeted CAR T-cell therapy (axi-cel, tisa-cel). The predictive and prognostic value of low vs. high metabolic tumor volume (MTV), total lesion glycolysis (TLG), and SUV were analyzed with cutoff values determined by the sample mean for MTV and TLG and mode for SUV. The response evaluation was conducted based on the post-CAR T best overall response, which was defined as the lowest disease burden measured on the PET scan at any time after CAR T-cell therapy. Univariate analysis was conducted using logistic regression, while the multivariate analysis was performed using logistic regression and Cox proportional hazards models, controlling for age ≥60, gender, CAR T product, and receiving bridging therapy. <h3>Results</h3> The median follow-up was 10.7 months (range, 0.6 - 46.5 months). The best objective overall response (complete response-CR and partial response) and CR rates post-CAR T were 78% (n=49) and 54% (n=34), respectively. On univariate analysis, low pre-CAR T TLG and MTV were predictive of CR post-CAR T (OR=4.7, p=0.01, OR=8.03, p=0.001, respectively). Patients with high pre-CAR T TLG or MTV had an increased risk of mortality (OR=3.6, p=0.03, OR=4.04, p=0.02), and a high pre-CAR T TLG was associated with a non-significant trend of increased grade 3-4 neurological events (OR=2.8, p=0.2). There was also a trend to shorter OS among patients with high SUVmax pre-CAR T (8.3 months vs. 24.4 months, p=0.3). On multivariate analysis, bulky disease (≥5 cm) (HR=6.08, 95% CI: 2.6-14.2, p=< 0.001), high MTV (HR=2.4, 95% CI: 1.13-4.9, p=0.022), and high TLG (HR=2.35, 95% CI: 1.1-5.0, p=0.026) were significantly associated with inferior OS. <h3>Conclusion</h3> High pre-CAR T MTV and TLG values are significantly associated with inferior CR and OS rates and a trend toward higher risk of severe neurotoxicity among patients with LBCL treated with CAR T-cell therapy. Bulky disease (≥ 5 cm) is associated with significantly inferior OS. These data suggest that there may be a role for pre- CAR T radiation therapy targeting bulky site(s) with high FDG avidity, regardless of symptoms, thereby reducing disease burden prior to CAR-T cell therapy, which may lead to improved efficacy and reduced CAR T-related adverse events.