Analysis of PET-CT Derived Radiomic Biomarkers with Efficacy, Safety, and Expansion of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed or Refractory Large B-Cell Lymphoma (LBCL)

Introduction In LBCL, presence of bulky disease is known to be an adverse prognostic factor, indicating poorer outcomes. We studied the association of radiomic biomarkers with efficacy, toxicity, and CAR T expansion in this single institution retrospective study of patients with LBCL who received axi-cel. Methods 189 patients with relapsed or refractory LBCL who were treated with axi-cel from 12/2017 to 5/2022 were studied. The closest PET-CT scan to CAR T leukapheresis date was identified for each patient. After excluding cases with unavailable pre-apheresis PET-CT scans, 172 patients were included in the analysis. Two reviewers independently used a semi-automated contouring software (MIM, v. 7.1.2) to measure maximum standardized uptake value (SUV Max), mean SUV, and total metabolic tumor volume (MTV) values of malignant lesions. CD19 CAR T expansion was measured by real-time flow cytometry with anti-idiotype-FMC63 conjugated to Dylight 65013. Areas under the curve (AUCs) were calculated for CAR T expansion in the 28 days following infusion using the linear trapezoidal method, then log base-10 transforming the result. Patients were categorized into high and low biomarker groups based on an optimal cutpoint, which was obtained using a maximally selected rank statistics approach. Progression-free survival (PFS) was used as the outcome of interest in creation of the binary discrimination.For univariate analyses, continuous variables were compared using a Mann-Whitney U-test, categorical using a Chi-square test, and time-to-event using a log-rank test. Results Median duration of follow up was 33 months (IQR: 17.9, 44.7). The optimal cut point for the MTV biomarker was found to be 134.38ml. High MTV (>134.38ml) was associated with bulky disease defined as >10cm (p<0.01), high IPI at apheresis (p<0.01), bridging treatment (p<0.01), pre-lymphodepletion lactate dehydrogenase (p<0.01), but was not associated with autologous stem cell transplant (p=0.34).Complete response (CR) rate was greater for those in the low MTV group (75.4%) compared to high MTV group (40.43%) p<0.01). Low MTV was significantly associated with better PFS (p=0.03); median PFS was 44.8 months (IQR 23.2,NA) for low MTV versus 3.2 months (IQR 2.9,6.1) for high MTV. Low MTV was also significantly associated with better overall survival (OS) (p<0.01); median OS was not reached for the low MTV group but was 18 months for the high MTV group (IQR 8.6,NA) (Figure 1).The proportion of those with severe grade ICANS, length of stay, and use of tocilizumab were significantly higher for those with high MTV (Table 1). There was no significant difference in CAR T expansion as measured by AUC between high and low MTV. Conclusion Our study demonstrates poor outcomes for efficacy, safety and healthcare utilization endpoints in with patients with high tumor bulk as measured by volumetric tumor assessment on PET-CT.