CAR-T can reduce the risk of death in patients with refractory LBCL by 73% compared with standard salvage treatment

LBCL is the most common subtype of non-Hodgkin's lymphoma.
Over the past few decades, the overall survival (OS) rate of LBCL in the United States and Europe has improved
.

However, the prognosis of patients with relapsed or refractory LBCL (R/R LBCL) is still poor and there are few potential curative options
.

Among refractory patients who progress during the initial immunochemotherapy or within 1 year after the first remission, only 30%-40% of patients respond to salvage chemotherapy, and may subsequently receive autologous hematopoietic stem cell transplantation (ASCT) consolidation therapy
.

The results of an international retrospective study of SCHOLAR-1 showed that patients with refractory LBCL who received conventional salvage chemotherapy had poorer clinical outcomes and poor survival
.

Axi-cel is an autologous CD19-targeted chimeric antigen receptor (CAR)-T cell therapy.
The key phase I/II ZUMA-1 study results confirmed its long-lasting remission in patients with refractory LBCL
.

Based on this, some researchers compared the 2-year clinical outcomes of refractory LBCL patients in the SCHOLAR-1 and ZUMA-1 studies, aiming to compare the clinical outcomes of standard rescue treatment and CAR-T cell therapy in refractory LBCL patients
.

Research methods The design and cohort details of the SCHOLAR-1 study have been reported in the early stage.
Data of refractory LBCL patients were collected from 4 cohorts (N = 636), including 2 observational cohorts and 2 large, phase 3, randomized controls Experiment
.

ZUMA-1 is a single-arm, multi-center, phase I/II study of Axi-cel in the treatment of refractory LBCL (including diffuse LBCL, primary mediastinal B-cell lymphoma and transformed follicular lymphoma)
.

Before comparing clinical outcomes, use propensity scores to establish a balance between patients in the ZUMA-1 and SCHOLAR-1 studies
.

Study results Patient demographics and baseline characteristics are in the key phase II part of the ZUMA-1 study.
101 patients received Axi-cel treatment, and the remission and survival can be evaluated
.

In the SCHOLAR-1 study, 434 and 424 patients were evaluated for remission and survival
.

The demographic and baseline characteristics of the patients in the two studies are detailed in Table 1
.

ZUMA-1 has more lines of treatment than patients in the SCHOLAR-1 study
.

The proportion of men in the ZUMA-1 and SCHOLAR-1 studies was similar, and the proportion of patients ≥65 years of age in the ZUMA-1 study was higher
.

Table 1: Comparison of patients' baseline characteristics for remission and survival in the ZUMA-1 and SCHOLAR-1 studies.
Patient remission.
The ORR and complete remission (CR) rates of patients in the ZUMA-1 study were 83% and 54%, respectively; The ORR and CR rates of patients in the SCHOLAR-1 study were 34% and 12%, respectively (Table 2)
.

In addition, the standardized comparison of ORR and CR rates strongly supports the use of Axi-cel in patients with refractory LBCL
.

Table 2: Remission status of patients in the ZUMA-1 and SCHOLAR-1 studies.
Survival status of patients in the ZUMA-1 study.
The median follow-up time of the ZUMA-1 study was 27.
1 months, and the median OS was 31.
0 months (95% CI: 11.
5 months-impossible to estimate )
.

The median follow-up time of each cohort of the entire SCHOLAR-1 study ranged from 7.
6 to 14.
8 years, and the patient's median OS was 5.
4 months (95% CI: 4.
6-6.
3 months)
.

The 2-year OS rate of patients in the ZUMA-1 study was 54% (95% CI: 30%-80%), and the 2-year OS rate of patients in the SCHOLAR-1 study was 20% (95% CI: 16%-%26 %); Compared with the standard salvage treatment in the SCHOLAR1 study, CAR-T cell therapy in the ZUMA-1 study can reduce the risk of death in patients with refractory LBCL by 73% (Table 3)
.

In a standardized analysis, the median OS of the patients in the ZUMA-1 study did not reach (27.
1 months of follow-up; 95% CI: 11.
5 months-unable to estimate), but the median OS of the patients in the SCHOLAR-1 study was 4.
1 months (95 % CI: 3.
5-5.
1 months)
.

Table 3: Subgroup analysis of the OS rate and median OS of patients in the ZUMA-1 and SCHOLAR-1 studies.
It is worth noting that although the number of ZUMA-1 patients is small, for patients who relapse and are refractory after ASCT, ZUMA The 2-year OS rate of patients in the -1 study was significantly higher than that of patients in the SCHOLAR-1 study, which were 50% and 22%, respectively
.

For patients who had previously received more than or equal to 2 lines of treatment and subsequently received ASCT, similar 2-year OS rates were observed in the ZUMA-1 and SCHOLAR-1 studies, which were 40% and 42%, respectively
.

Research conclusions Although the study is a non-randomized analysis and has certain limitations, the results of the study show that CAR-T cell therapy produces durable remission and significant survival gains in patients with refractory LBCL compared with standard salvage therapy.
Benefit
.

References: Sattva S Neelapu, Frederick L Locke, Nancy L Bartlett, et al.
Comparison of 2-year outcomes with CAR T cells (ZUMA-1) versus salvage chemotherapy in refractory large B-cell lymphoma.
Blood Adv.
2021 Oct 26 ;5(20):4149-4155.
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