Association of Metabolic Tumor Volume and Clinical Outcomes in the ZUMA-7 Study

ZUMA-7 (NCT03391466), the phase 3 study of axicabtagene ciloleucel (axi-cel) versus standard of care (SOC) in second-line large B-cell lymphoma (LBCL), found axi-cel to be superior to SOC across common prognostic groups, including tumor burden (TB), as calculated by the sum of product diameters (SPD), and lactate dehydrogenase (LDH); however, TB can also be measured by metabolic tumor volume (MTV) using fluorodeoxyglucose (FDG) positron emission tomography (PET)–computed tomography scans, which has previously been shown to correlate with clinical outcomes in patients with relapsed or refractory LBCL given chimeric antigen receptor T-cell therapy in the third-line setting. Clinical outcomes by MTV from the ZUMA-7 study were presented at the 64th American Society of Hematology Annual Meeting and Exposition.

MTV was obtained from the attenuation-corrected whole-body FDG PET scans at screening, with whole tumor volumes of interest superimposed on tumors using a predefined approach. MTV was calculated as the number of volumetric pixels, or voxels, with standardized uptake value (SUV) measurements of 41%-100% of tumor SUV_max and reported as MTV_total (mL) per patient. Associations between MTV, baseline characteristics, and clinical outcomes were assessed using descriptive statistics.

A total of 341 patients were evaluated for MTV (axi-cel, 176; SOC, 165), with a median MTV of 228.1 mL (range, 2.3-16,669.3) in axi-cel patients, 231.9 mL (range, 0.04-2811.2) in SOC patients, and 230.2 mL (range, 0.04-16,669.3) overall. Median MTV was higher in patients who were <65 years of age (n = 236; 255.2 mL [range, 0.04-16,669.3]) versus patients who were ≥65 years (n = 105; 176.7 mL [range, 6.8-4101.8]). Median MTV was higher in patients with elevated LDH (n = 185; 371.2 mL [range, 2.3-16,669.3]) versus patients with normal LDH (n = 156; 123.9 mL [range, 0.04-3712.8]). MTV was also positively associated with SPD (n = 308; Spearman’s rho correlation of 0.523; 95% confidence interval [CI], 0.436-0.599) and LDH (n = 341; Spearman’s rho correlation of 0.452; 95% CI, 0.362-0.532).

Axi-cel event-free survival (EFS) was superior to SOC for both low MTV (≤median; hazard ratio [HR], 0.423; 95% CI, 0.288-0.620) and high MTV (>median; HR, 0.417; 95% CI, 0.293-0.592). EFS was shorter in axi-cel patients with high MTV (HR, 1.441; 95% CI, 0.978-2.124) and in SOC patients with high MTV (HR, 1.486; 95% CI, 1.055-2.093). Axi-cel progression-free survival (PFS) was superior to SOC for both low MTV (HR, 0.504; 95% CI, 0.328-0.776) and high MTV (HR, 0.523; 95% CI, 0.357-0.765).

PFS was shorter in axi-cel patients with high MTV (HR, 1.644; 95% CI, 1.090-2.480) and in SOC patients with high MTV (HR, 1.635; 95% CI, 1.098-2.433). In axi-cel patients, median MTV was higher for patients who experienced grade ≥3 neurologic events (NEs; n = 36) versus patients who experienced grade 1-2 or no NEs (n = 134; P = .0224). Median MTV was higher for axi-cel patients who experienced grade ≥3 cytokine release syndrome (CRS; n = 11) compared with patients who experienced grade 1-2 or no CRS (n = 159; P = .0126).

Axi-cel was found to be superior to SOC regardless of MTV subgroup. Low MTV was associated with better outcomes with axi-cel versus high MTV, and rates of grade ≥3 NEs and CRS were associated with higher MTV. These findings suggest that MTV may be a better prognostic marker than SPD.

Source

Locke FL, Oluwole OO, Kuruvilla J, et al. Association of metabolic tumor volume and clinical outcomes in second-line relapsed/refractory large B-cell lymphoma following axicabtagene ciloleucel versus standard-of-care therapy in ZUMA-7. Presented at: 64th American Society of Hematology Annual Meeting and Exposition, December 10-13, 2022; New Orleans, LA. Oral presentation 259.