KEY TAKEAWAYS
- The ZUMA-12 trial is a multicenter, open-label, single-arm, phase II trial that evaluated the safety and efficacy of axi-cel for the frontline treatment of high-grade confirmed LBCL.
- The trial’s primary aim was to determine the objective and complete response rates of axi-cel in LBCL patients.
- The trial included 42 patients from the USA, Australia, and France and demonstrated the safety of axi-cel for the frontline treatment of high-grade LBCL.
- CAR T-cell expansion was seen in all 40 patients who received axi-cel infusion, with a median time to peak circulating CAR T-cells of 8 days.
- Grade 3 elevated interleukin-5, macrophage inflammatory protein-1α, interferon-, ferritin, tumour necrosis factor-α, interleukin-10, interleukin-8, and programmed death-ligand 1.
Adult patients with high-grade confirmed LBCL are being studied in a phase II trial that is multicenter, open-label, and single-arm. The presence of MYC and BCL2 and/or BCL6 translocations or an International Prognostic Index of 3 or higher at any time before enrollment was considered high grade. You can read more about the methodology used in this study here. Between February 6, 2019, and October 22, 2020, 42 patients were enrolled, and 40 received an axi-cel infusion. The efficacy analysis included 37 patients, while the safety analysis included 40 patients (median follow-up, 17.4 months; range, 6.0-26.7 months) (median follow-up, 15.9 months; range, 6.0–26.7 months). Patient accrual is complete; participants were gathered from the United States (n = 33), Australia (n = 7), and France (n = 2).
Expansion of CAR T cells was observed in all 40 patients. The peak levels of circulating CAR T-cells were reached in a median of 8 days (8–37 days). The median peak concentration of CAR T cells was 36.27 cells µl-1. No statistical significance was found between median peak levels of CAR T-cells in patients who relapsed/did not respond and those with an ongoing response to axi-cel. Several cytokines were found to be at least doubled in patients who experienced Grade ≥3 neurological events, including interleukin (IL)-5, macrophage inflammatory protein-1α (MIP-1α), interferon (IFN)-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), ferritin, tumor necrosis factor (TNF)-α, IL-10, IL-8, and programmed death-ligand 1 (PDL1) (p < 0.05).
Among first-line treatments for high-grade LBCL, axi-cel shows promise based on the primary analysis of the ZUMA-12 phase II trial. CAR T-cell expansion was documented in all study participants, including 37 patients with evaluable efficacy. The objective response rate was 89%, and the complete response rate was 78%. Adverse events and toxicities are manageable, consistent with the safety data from previous axi-cel studies. Further comparison of efficacy and safety data with the current standard of care requires larger, randomized control studies to replicate these results in larger study populations.
Source: https://lymphomahub.com/medical-information/zuma-12-primary-analysis-axi-cel-for-the-frontline-treatment-for-high-risk-lbcl
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03761056
Neelapu, et al. ZUMA-12 primary analysis: Axi-cel for the frontline treatment for high-risk LBCL.
