Axi-cel Shows Improved Quality-Adjusted Survival Versus Standard of Care in LBCL

A recent post hoc analysis of data from the ZUMA-7 trial (NCT03391466) found that axicabtagene ciloleucel (axi-cel) was associated with better quality-adjusted time without symptoms or toxicity (Q-TWiST) versus the standard of care in relapsed or refractory (R/R) large B-cell lymphoma (LBCL).

In the randomized, phase 3 ZUMA-7 trial, axi-cel showed improved event-free survival time and response rates versus salvage chemotherapy and autologous stem cell transplant (ASCT), which was previously the only option available for patients with R/R LBCL after frontline chemoimmunotherapy. Based on these findings, axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, was granted FDA approval for use in this patient population in 2022.

The pre-planned post hoc analysis, which was published online ahead of print in Transplantation and Cellular Therapy, aimed to determine the quality-adjusted survival outcomes of axi-cel versus the standard of care. The Q-TWiST method estimates “net health benefits” by stratifying survival time into distinct health states, then calculating the amount and quality of time spent in each state. This allows researchers to adjust patients’ survival time to factor in quality of life (QOL).

Event-free survival (EFS) and adverse event (AE) data were used to separate overall survival (OS) into 3 states: the time with grade 3 or higher AEs prior to an event of interest (TOX), time spent without severe toxicity or progression (TWiST), and time from an event until death or the end of follow-up (REL). The overall Q-TWiST was calculated as a weighted sum of mean TOX, TWiST, and REL based on QOL utility scores for each health state.

The axi-cel cohort showed a mean TWiST duration of 11.2 months, versus 5.4 months in the standard of care cohort at 23.5 months of follow-up. The mean TOX was 1.2 months in the axi-cel cohort versus .74 months in the standard of care cohort, and the mean REL in the axi-cel cohort was 6.1 months versus 10.7 months in the standard of care cohort.

In the axi-cel group, quality-adjusted survival was 3.7 months longer than in the standard of care group, amounting to a 21.9% relative gain. Based on established classification, a relative gain of 10% would be considered “clinically important,” and 15% or more would be “clearly clinically important.”

Q-TWiST gains were an estimated 3.1 months in those younger than 65 years of age and 5.2 months for those aged 65 years or older. In patients with primary refractory disease, relapse within 6 months, and relapse between 6 and 12 months, estimated Q-TWiST gains were 3.2 months, 9.1 months, and 4.1 months, respectively.

Despite relative declines in QOL associated with treatment toxicity, disease progression, or additional cancer therapy, the study found axi-cel treatment to be associated with Q-TWiST gains versus the chemotherapy and ASCT in R/R LBCL. These gains were most significant in patients not bothered by AEs and who strongly prefer to avoid EFS events. However, the gain was still positive in patients who have a strong preference to avoid AEs and who are not bothered by EFS events.

Q-TWiST gains were also more significant in patients 65 years and older versus younger patients, which is in line with data from ZUMA-7 suggesting that axi-cel carries a greater benefit in this population.

“Overall, this demonstrates that axi-cel is an effective second-line therapy and results in even greater quality-adjusted survival in the elderly with R/R LBCL, for whom new treatment options are needed given that elderly patients may not qualify for transplantation in certain regions of the world,” the authors wrote.

The Q-TWiST analysis suggests axi-cel in the second line is beneficial and a viable treatment option for patients whose LBCL is refractory to first-line chemoimmunotherapy and those who relapse after chemoimmunotherapy.

Reference

Kersten MJ, Qiao Y, Shah R, et al. Quality-adjusted time without symptoms or toxicity: analysis of axicabtagene ciloleucel versus standard of care in patients with relapsed/refractory large B-cell lymphoma: Q-TWiST analysis of axi-cel versus standard of care. Transplant Cell Ther. Published online January 13, 2023. doi:10.1016/j.jtct.2023.01.008