Patient-reported outcomes in phase III ZUMA-7 trial: axicabtagene versus standard of care in R/R LBCL

Introduction

Relapsed/refractory (R/R) large B-cell lymphoma (LBCL) is a high-risk lymphoma associated with poor prognosis and treatment outcomes. Additionally, around 50% of patients with R/R LBCL are ineligible for a second-line standard of care (SOC) high-dose chemotherapy and allogeneic stem cell transplantation. The introduction of CAR T-cell therapies such as axicabtagene ciloleucel (axi-cel) as a third-line therapy has greatly improved clinical practice in these populations; however, there has been a shift in treatment as recent data reveal the promising potential of CAR T-cell therapy as second-line therapy for the treatment of patients with R/R LBCL.¹

The Lymphoma Hub previously published an article on the primary analysis results of phase III ZUMA-7 trial (NCT03391466). Below, we summarize the recently published article by Elsawy M, et al. in Blood on patient-reported outcomes (PRO) of the ZUMA-7 trial.²

Study design

For the 296 people included in the QoL analysis set, eligible patients were:

• ≥18 years of age with histologically diagnosed LBCL per World Health Organization (WHO) 2016 criteria;
• R/R within 12 months of first-line chemoimmunotherapy, including an anti-CD20 monoclonal antibody and anthracycline-containing regimen; and
• anticipated to receive high-dose chemotherapy and allogenic stem cell transplantation if they achieved a successful response to initial chemoimmunotherapy.

The following PRO instruments were administered at baseline, Day 50, Day 100, Day 150, Month 9, every 3 months up until Month 24, or until disease progression, death, or new lymphoma therapy: European organization for research and treatment of cancer Quality of Life Questionnaire Core 30 (EORTCQLQ-C30), EuroQol 5-Dimension 5-Level (EQ-5D-5L), and the Work Productivity and Activity Impairment Questionnaire: General Health version 2.0 (WPAI:GH version v2.0).

The prespecified secondary endpoints were global health status and physical functioning by EORTC QLQ-C30, and visual analogue score (VAS) by EQ-5D-5L. Additional exploratory endpoints included other domains of EORTC QLQ-C30, EQ-5D-5L health index score, and WPAI:GH v2.0. Details of the assessments are summarized in Table 1.

Table 1. PRO instruments used to assess QoL in patients with LBCL*

Results

Baseline characteristics

Baseline characteristics for the 296 patients included in the QoL analysis set are summarized in Table 2.

Table 2. Selected baseline and demographic characteristics for axi-cel vs SOC cohort*

Patient-reported outcomes

A statistically significant and clinically meaningful difference between the mean change in scores from baseline was observed at Day 100 for the prespecified endpoints, favoring axi-cel over SOC (Table 3). Similarly, improvements in the mean change in EORTC global health status and 5Q-VAS scores from baseline were observed favoring axi-cel over SOC on Day 150. However, the difference was only clinically meaningful for EQ-5D-5L VAS. Overall, axi-cel surpassed the mean estimated scores at baseline by Day 150 for PROs compared to Month 9 or later for the SOC cohort.

Table 3. Estimated score differences from baseline to Day 100 and Day 150 for prespecified PRO*

Improvements were also seen in axi-cel over SOC for the secondary and additional exploratory endpoints for other domains of EORTC QLQ-C30, EQ-5D-5L index, and WPAI:GH. Mean differences in scores from baseline favored axi-cel over SOC on Day 100 for nausea and vomiting, diarrhea, insomnia, appetite loss, role, and social functioning by EORTC QLQ-C30, Day 150 for role functioning and fatigue by EORTC QLQ-C30, and Month 9 for EORTC QLQ-C30 dyspnea. For WPAI:GH, significantly lower abseentism and lower mean activities impairments were seen at Day 100 for axi-cel over SOC.

Conclusion

This comparative analysis of patient-reported outcomes in the ZUMA-7 study highlights the importance of QoL assessments and patient experiences to fully elucidate the therapeutic potential of treatments. Axi-cel showed a statistically significant, clinically meaningful improvement and a faster recovery rate to baseline QoL over SOC by Day 100 and Day 150 for multiple PRO scores. Despite some methodological issues, as well as disproportionality in sample sizes and patient characteristics in this study, sensitivity analyses have confirmed the success of axi-cel over SOC. With both higher efficacy and QoL outcomes over SOC, axi-cel shows its promising benefit as a future second-line treatment for patients with R/R LBCL.