Axicabtagene ciloleucel vs standard of care in second-line large B-cell lymphoma: outcomes by metabolic tumor volume

Abstract

Metabolic tumor volume (MTV) assessed using 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography, a measure of tumor burden, is a promising prognostic indicator in large B-cell lymphoma (LBCL). This exploratory analysis evaluated relationships between baseline MTV (categorized as low [median or less] vs high [greater than median]) and clinical outcomes in the phase 3 ZUMA-7 study (NCT03391466). Patients with LBCL relapsed within 12 months of or refractory to first-line chemoimmunotherapy were randomized 1:1 to axicabtagene ciloleucel (axi-cel; autologous anti-CD19 chimeric antigen receptor T-cell therapy) or standard care (2-3 cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem cell transplantation in patients who had a response). All P values are descriptive. Within high- and low-MTV subgroups, event-free survival (EFS) and progression-free survival (PFS) were superior with axi-cel vs standard care. EFS in patients with high MTV (vs low MTV) was numerically shorter with axi-cel and was significantly shorter with standard care. PFS was shorter in patients with high MTV vs low MTV in both the axi-cel and standard-care arms, and median MTV was lower in patients in ongoing response at data cutoff vs others. Median MTV was higher in patients treated with axi-cel who experienced grade ≥3 neurologic events or cytokine release syndrome (CRS) than in patients with grade 1/2 or no neurologic events or CRS, respectively. Baseline MTV less than or equal to median was associated with better clinical outcomes in patients receiving axi-cel or standard care for second-line LBCL. The trial was registered at www.clinicaltrials.gov as #NCT03391466.

Graphical abstract

Figure 1.

Baseline MTV estimates from whole-body FDG PET images. Single-slice coronal FDG PET images (A,E) demonstrating hypermetabolic uptake in the original image data sets. (A-D) Hypermetabolic FDG uptake in a limited number of lesions in the abdomen and pelvis with an estimated total whole-body MTV of 231.9 mL. (E-H) Hypermetabolic FDG uptake in soft-tissue and nodal lesions in the chest and abdomen with an estimated total whole-body MTV of 1921.7 mL. The segmented lesions containing the individual lesion masks (colored regions in panels B,F) are shown. Within each of these segmented lesions, masks of the FDG PET voxels with SUV values 41% to 100% of SUVmax are delineated on the parametric maps (C,G). The total whole-body MTV is then calculated from the sum of delineated voxels. The arrows represent normal physiologic activity in the bladder (A,E) and gastrointestinal tract (A). Panels D,H are maximum intensity projection images that represent the extent of disease on the whole-body FDG PET.

Figure 2.

Associations between baseline MTV and known prognostic factors. Spearman correlation estimates and P values from a Fisher z transformation were used to summarize relationships between baseline MTV and continuous baseline covariates. (A) Baseline SPD vs MTV. (B) Baseline LDH vs MTV. The fit line is based on linear regression with 95% CI limit.

Figure 3.

Kaplan-Meier plots of survival outcomes by MTV and treatment arm. (A) EFS per central assessment. (B) PFS per investigator assessment. Estimated HRs, 95% CIs, and descriptive 2-sided P values were calculated from a Cox proportional-hazards model.

Figure 4.

Baseline MTV by response group and treatment arm. (A) Responders vs nonresponders per central assessment. (B) Patients with ongoing response vs others per central assessment. Descriptive 2-sided P values for 2-group comparisons were calculated using Wilcoxon rank sum test. Extreme values are not shown.

Figure 5.

Baseline MTV by grade of neurologic events and CRS in patients treated with axi-cel. (A) Neurologic events. (B) CRS. Descriptive 2-sided P values for 2-group comparisons were calculated using the Wilcoxon rank sum test. Extreme values are not shown.