How Does Metabolic Tumor Volume Affect Responses to Axi-Cel in LBCL?

Predicting which patients will have the best responses to chimeric antigen receptor (CAR) T-cell therapy based on their clinical features remains a work in progress. Data just published in the journal Blood examined the effect of metabolic tumor volume (MTV), a prognostic indicator in large B-cell lymphoma (LBCL).

Fred Locke, MD | Image credit: Moffitt Cancer Center

“High tumor burden has long been recognized as an independent risk factor for outcomes in LBCL and other lymphomas,” said the authors, led by Frederick Locke, MD, of H. Lee Moffitt Cancer Center and lead author of the landmark ZUMA-7 trial (NCT03391466). Although tumor segmentation and measurement has evolved—including some uses in treatment planning—there is no standard procedure for quantifying tumor burden in lymphoma, they wrote.

The authors culled patient data from ZUMA-7, which in December 2021 showed the that the CAR T-cell therapy axicabtagene ciloleucel (axi-cel, Yescarta) produced superior event-free survival compared with standard of care. Their exploratory analysis assessed the relationship between baseline MTV and outcomes, both for patients treated with axi-cel, which was the trial’s treatment arm, and the chemoimmunotherapy standard of care arm.

MTV was assessed using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET). Patients were divided as low [≤median] vs high [>median]) MTV at baseline, with their clinical outcomes then assessed based on results of the phase 3 ZUMA-7 study, which included patients with LBCL who had relapsed within 12 months or were refractory to first-line chemoimmunotherapy.

The authors explained the MTV assessment during the screening process. “Our procedures for MTV determination were carried out with a predefined and consistent methodology across patients, similar to that employed by others. Briefly, whole-body FDG PET-CT scans were performed in ZUMA-7 patients who underwent at least a 4-hour fast before FDG administration,” they wrote. Eligible patients received FDG and subsequently received PET scans. The authors additionally outline their algorithm and use of International Prognostic Index categories to stratify the patients.

Results were as follows:

• For patients with both the high and low MTV, event-free survival (EFS) and progression-free survival (PFS) were superior with axi-cel vs standard care (all HR ≤0.523; P <.01).
• EFS among patients with high MTV, compared with low MTV, was numerically shorter with axi-cel (HR, 1.448; P = .06) and was significantly shorter with standard care (HR, 1.486; P = .02).
• PFS was shorter among patients with high MTV compared with low MTV in both the axi-cel arm (HR, 1.660; P = .02), and the standard-care arm (HR, 1.635; P = .02). The median MTV was lower in patients who were still experiencing a response at the data cutoff vs others (both P ≤ .01).
• Among patients treated with axi-cel, median MTV was higher in patients 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 (P ≤ .03).

The authors noted the limitations of their findings. “The current analysis is limited because it was not prespecified and therefore not statistically powered for definitive conclusions,” they wrote. Furthermore, alternative methods of MTV determination and alternative analyses that incorporate morphology, intensity, or special distribution of lesions, and/or a different threshold for categorizing high vs low MTV might have yielded different results when applied to the ZUMA-7 dataset.

“For example, a more time-consuming manual approach to MTV determination may provide more accuracy regarding tumor burden.”

Although the authors say standardization of MTV assessment is needed before such analyses could be used more broadly, they conclude, “Baseline MTV of less than or equal to the median was associated with better clinical outcomes in patients receiving axi-cel or standard care for second-line LBCL.”

Reference

Locke FL, Oluwole OO, Kuruvilla J, et al. Axicabtagene ciloleucel versus standard of care in second-line large B-cell lymphoma: outcomes by metabolic tumor volume. Blood. 2024. Published online April 1, 2024. https://doi.org/10.1182/blood.2023021620