A New Hope! The FDA approved Axi-cel for the second-line treatment of large B-cell lymphoma

Image: Pexels | Written by: Medical Companion Travel Content Team

Original articles, please do not reprint without permission

Based on good efficacy and safety, the FDA has approved Axi-cel for the treatment of adult patients with refractory first-line immunotherapy or relapsing within 12 months of first-line immunotherapy.

I. Overview

The FDA approved axiabtagene ciloleucel (abbreviated as axi-cel, trade name Yescarta) for the treatment of adult patients with large B-cell lymphoma who are refractory to treatment with first-line immunotherapy or who relapse within 12 months of first-line immunochemotherapy.

1. Introduction to large B-cell lymphoma (LBCL) and the status quo of second-line treatment

Large B-cell lymphoma is a highly heterogeneous malignancy that accounts for 40% to 45% of the total number of non-Hodgkin lymphoma patients in mainland China. About 30% to 40% of patients with large B-cell lymphoma develop recurrent refractory large B-cell lymphoma after first-line therapy.

High-dose chemotherapy plus autologous stem cell transplantation is recommended as the standard second-line treatment option for patients with relapsed/refractory large B-cell lymphoma. However, some disease characteristics limit the effect of the drug, such as primary refractory, age-adjusted international prognosis index is high risk, accompanied by double or triple strike genetic variation, etc. Eventually, only 40% to 50% of patients responded to second-line therapy and were able to undergo autologous stem cell transplantation (HDT-ASCT), and the prognosis of these patients was poor, with about 50% of patients relapsing after transplantation and long-term survival rates ranging from 30% to 40%. Therefore, these patients urgently need new treatment options for second-line treatment that can improve prognosis.

2. Introduction and approval history of CAR-T therapy Axi-cel

Axi-cel is a CD19-targeted, genetically modified autologous T-cell immunotherapy with CD3ζ/CD28 signaling pathway.

2. Clinical trials

The primary endpoints of the trial were event-free survival as evaluated by the blinded center, with primary secondary endpoints including objective response rate, overall survival, progression-free survival, patient-reported outcomes, and safety.

A total of 359 patients were included in the trial, with a median age of 59 years and 30% of patients aged 65 years or older. 74% of patients had primary refractory treatment for first-line therapy, and 26% relapsed within 1 year of previous treatment. 16% of patients had high-grade B-cell lymphoma, 33% had dual-expressing lymphoma, 6% had MYC rearrangement, and 54% had elevated lactate dehydrogenase levels.

They were randomly grouped on a 1:1 ratio, with one group (n=180) receiving a single infusion of axi-cel and the other (n=179) receiving standard therapy in the form of platinum-based chemotherapy.

Patients are initially evaluated for disease on day 50; patients treated with CAR-T cell therapy continue to receive day 100, day 150, and long-term follow-up. With regard to patients who respond to standard therapy, whether with a complete or partial response, autologous stem cell transplantation continues. Those who did not respond to treatment received additional treatment beyond the trial regimen.

1. Validity results

Results showed that the median event-free survival (EFS) was 8.3 months (95% CI, 4.5-15.8) in the Axi-cel treatment group and 2.0 months (95% CI, 1.6-2.8) in the standard therapy (SOC) group (HR, 0.4-; 95% CI, 0.31-0.51; P) in the standard treatment (SOC) group

Axi-cel also improved the objective response rate (ORR) compared to the standard treatment group, which was 83% (95% CI, 77%-88%) and 50% (95% CI, 43%-58%) (odds ratio, 5.31; 95% CI, 3.1-8.9; P

2. Security results

In terms of safety, 91% of patients treated with axi-cel had a grade 3 or more adverse reaction (AE), compared with 83% of patients in the standard treatment group. The most common grade 3 or higher adverse reactions include neutropenia (69% and 41%, respectively), anemia (30% and 39%, respectively) and leukopenia (29% and 22%, respectively).

Six percent of patients in the axi-cel treatment group developed cytokine release syndrome (CRS) of grade 3 or higher, with the most common symptoms including fever (99 percent), hypotension (43 percent), and sinus tachycardia (31 percent). The median time for the occurrence of this toxicity was 3 days and the median duration of the event was 7 days.

21% of patients in the axi-cel treatment group experienced a neurological event of grade 3 or more, compared to 1% in the standard-of-care group; the most common adverse events included tremor (26% in the axi-cel group and 1% in the SOC group), confused states (24% and 2%, respectively), and aphasia (21% and 0%, respectively). The median onset of onset was 7 days and 23 days for patients in the axi-cel treatment and standard treatment groups, respectively, and the median duration of events was 9 days and 23 days, respectively.

A total of 55 deaths were reported in the axi-cel treatment group, including disease progression (n=47), grade 5 adverse events (n=7) during the prescribed reporting period, and treatment-related deaths (n=1). 68 deaths were reported in the standard treatment group, and the number of cases with the same 3 causes of death as the trial group was 4, 2 and 2, respectively.

3. Improvements related to quality of life

Meanwhile, trial results presented at the 48th Annual Meeting of the EBMT showed that the benefit of quality of life was observed in patients with large B-cell lymphoma at day 100 after receiving Axi-cel as a second-line treatment regimen compared with standard therapy.

3. Summary

The ZUMA-7 trial showed that axi-cel was significantly better than standard therapy as a second-line treatment regimen for patients with large B-cell lymphoma, while improving the quality of life of patients. The FDA approval gives patients new hope that Axi-cel will play a more role.