Association of high baseline metabolic tumor volume with response following axicabtagene ciloleucel in refractory large B-cell lymphoma.

Abstract

7562 Background: Axicabtagene ciloleucel (axi-cel) is an anti-CD19 targeted Chimeric Antigen Receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL). High tumor burden, by sum of the product of diameters (SPD) in ≥ 6 reference lesions, was associated with lower durable responses rates in the ZUMA-1 trial (Locke F.L. ASCO. 2018). Although metabolic tumor volume (MTV) predicts worse outcomes with chemotherapy in lymphoma (Guo B. PLoSOne. 2019), its prognostic significance remains unclear with axi-cel therapy. Methods: MTV was measured by MIM Software using a 41% SUVmax threshold with manual lesion contour adjustment and radiologist review. Low and high MTV groups were defined based on median cutoff value. Cytokine release syndrome (CRS) was graded by Lee et al. ( Blood. 2014). Neurotoxicity (NT) was graded by CTCAEv4. Toxicities, overall response rate (ORR), and complete response rate (CR) were evaluated via Fisher’s test; PFS and OS via Kaplan-Meier and log-rank test. Results: 48 patients with LBCL, or its variants, that received axi-cel at Moffitt from June 2015 to October 2018 were included. 31 were male, and median age was 63 years (range, 28-76). CRS occurred in 43/47 (91.5%) and NT in 32/47 (68.1%) patients. Grade 3-4 CRS in 2/47 (4.3%) and NT in 12/47 (25.5%). Median follow up for survivors was 8.9 months (range, 1.4- 36.8 months). CR was achieved in 31/48 (64.6 %) and ORR in 39/48 (81.3%). Median for the low MTV group was 35.1 mL (range, 4.24-132.8 mL), and for the high MTV group 455.5 mL (range, 162.2-1221.4 mL). High MTV was not predictive of G1-4 NT or G3-4 NT (OR = 1.14, P = 0.99; OR = 1.66, P = 0.52). Similarly, high MTV was not predictive of G1-4 CRS or G3-4 CRS (OR = 0.29, P = 0.348; OR = 1.05, P = 0.99). Low MTV was predictive of ORR (OR = 11.50, P = 0.026) and CR (OR = 9.8, P = 0.002). Patients with high MTV had inferior PFS (HR = 3.296, 95% CI 1.42-7.64, P = 0.008) and OS (HR = 6.68, 95% CI 2.56-17.32, P = 0.003). Conclusions: High baseline MTV is associated with decreased and less durable response following axi-cel. As survival data mature, future analyses will aim to assess the role of MTV as an independent prognostic tool in axi-cel recipients with LBCL.