Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Axi-Cel Extends Relapsed/Refractory Large B-Cell Lymphoma EFS

Second-line anti-CD19 chimeric antigen receptor T-cell therapy offers alternative to standard chemoimmunotherapy and transplantation for large B-cell lymphoma
16 Dec 2021
Immunotherapy;  Lymphomas

Author: By Lynda Williams, Senior medwireNews Reporter 

 

medwireNews: ZUMA-7 trial findings demonstrate a significant event-free survival (EFS) benefit for patients with large B-cell lymphoma given second-line therapy with axicabtagene ciloleucel (axi-cel) compared with standard care. 

The research was presented at the 63rd American Society of Hematology Annual Meeting & Exposition in Atlanta, Georgia, USA, and simultaneously reported in The New England Journal of Medicine

“Axi-cel appears to be a viable alternative to a regimen of chemoimmunotherapy, high-dose chemotherapy, and autologous stem-cell transplantation for the second-line treatment of relapsed or refractory large B-cell lymphoma”, say Frederick Locke, from Moffitt Cancer Center in Tampa, Florida, USA, and co-authors. 

For the phase III trial, patients who had relapsed within 12 months of first-line chemoimmunotherapy or had refractory disease were randomly assigned to receive either the autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy axi-cel or standard care with 2–3 cycles of protocol-specified chemoimmunotherapy. Patients responding to chemoimmunotherapy were then scheduled to receive high-dose chemotherapy and autologous stem-cell transplantation. 

Overall, 170 of the 180 patients in the axi-cel group received their CAR T-cell infusion. Of the 179 patients in the standard care arm, 168 received at least one dose of salvage chemotherapy and 80 responded to the treatment; 69 underwent leukapheresis, 64 received high-dose chemotherapy and 62 underwent CD34+ stem-cell therapy. 

After a median 24.9 months of follow-up, the primary endpoint of median EFS was 8.3 months for the patients who were randomly assigned to receive axi-cel versus 2.0 months with standard care. The 24-month rate of EFS was significantly higher with axi-cel than standard care, with a hazard ratio (HR) for event or death of 0.40. 

In addition, 83% of the axi-cel group responded to treatment compared with 50% of the standard care group, with complete responses reported in 65% and 32% of patients, respectively. 

Median progression-free survival was significantly longer with axi-cel than standard care, at 14.7 versus 3.7 months and a HR of 0.47. The 2-year rates were 46% and 27%, respectively.  

Interim analysis showed that median overall survival (OS) was unreached with axi-cel and 35.1 months with standard care, with a HR for death of 0.73 that did not reach statistical significance. The 2-year rates of OS were 61% and 52%, respectively, with progressive disease-related deaths occurring in a corresponding 29% and 36% of the treatment arms. 

The researchers note that the OS analysis may have been confounded by the use of CAR T-cell therapy outside of the study protocol by 56% of the standard care arm who had not responded to treatment or experienced progressive disease. 

“The median overall survival in the standard-care group was longer than has been observed in historical studies”, they add, writing that “this finding is potentially due to the availability of newer agents, such as CAR T-cell therapy, that can be used in patients whose disease is refractory to or relapses after second-line therapy.”

Frederick Locke et al also highlight that 30% of patients in the ZUMA-7 study were aged at least 65 years, showing that “axi-cel can be an effective second-line therapeutic option in elderly patients who do not have clinically significant coexisting conditions.”

Grade 3 and more severe adverse events (AEs) occurred in 91% of the axi-cel arm and 83% of the standard care am, including infection in 14% versus 11%, and serious AEs of any grade were reported for 50% versus 46%.  

Grade 3 or more severe neurological events occurred in 21% of patients given axi-cel and 1% of controls, after a median of 7 and 23 days, respectively, with no related deaths. 

Among patients given axi-cel, 92% experienced cytokine release syndrome (CRS) a median of 3 days after infusion and 6% had grade 3 or more severe CRS; 65% received tocilizumab, 24% glucocorticoids and 6% vasopressors, and there were no CRS-related deaths. 

Frederick Locke et al summarise: “Treatment with axi-cel induced high-grade adverse events in the vast majority of patients, but few patients had fatal effects from treatment and the magnitude of the toxicity was consistent with previous reports in third-line therapy, although unique problems attend CAR T-cell therapy.” 

References  

Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med; Advance online publication 11 December 2021. Doi: 10.1056/NEJMoa2116133 

Locke FL, Miklos DB, Jacobson CA, et al. Primary Analysis of ZUMA7: A Phase 3 Randomized Trial of Axicabtagene Ciloleucel (Axi-Cel) Versus StandardofCare Therapy in Patients with Relapsed/Refractory Large B-Cell Lymphoma. Abstract 2. 63rd American Society of Hematology Annual Meeting & Exposition; Atlanta, Georgia, USA: 11–14 December 2021 

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2021 Springer Healthcare part of the Springer Nature group

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.