Second-line Axi-cel Elicits OS Benefit in Relapsed/Refractory LBCL

Axicabtagene ciloleucel (axi-cel; Yescarta) produced a statistically significant improvement in overall survival (OS) compared with standard-of-care (SOC) therapy in patients with relapsed/refractory large B-cell lymphoma (LBCL) within 12 months of completion of first-line therapy, according to data from the primary OS analysis of the phase 3 ZUMA-7 trial (NCT03391466).¹

Investigators plan to present full results from the OS analysis at an upcoming medical meeting.

Prior data from ZUMA-7 supported the FDA approval of axi-cel for the treatment of adult patients with LBCL that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy in April 2022.²

Findings for the primary end point of event-free survival (EFS) showed that at a median follow-up of 24.9 months, axi-cel generated an estimated median EFS of 8.3 months (95% CI, 4.5-15.8) compared with 2.0 months (95% CI, 1.6-2.8) with SOC treatment (HR, 0.40; 95% CI, 0.31-0.51; P <.0001). The estimated 18-month EFS rates in the experimental and control arms were 41.5% (95% CI, 34.2%-48.6%) and 17.0% (95% CI, 11.8%-23.0%), respectively.

Additionally, axi-cel elicited an objective response rate (ORR) of 83% (95% CI, 77%-88%) vs 50% (95% CI, 43%-58%) for SOC.

The randomized, open-label, global, multicenter, phase 3 ZUMA-7 study enrolled 359 patients with relapsed/refractory LBCL within 12 months of first-line therapy.³ First-line treatment needed to consist of an anti-CD20 monoclonal antibody, unless the investigator determined that tumor was CD20 negative, and an anthracycline-containing chemotherapy regimen.

Patients were excluded from the trial if they had a history of malignancy other than non-melanoma skin cancer or carcinoma in situ unless they were disease free for at least 3 years; received more than 1 line of therapy for LBCL; or had a history of autologous or allogeneic stem cell transplant.

Patients were randomly assigned 1:1 to a single infusion of axi-cel or SOC treatment with platinum-containing salvage chemotherapy followed by high-dose therapy and autologous stem cell transplant in responders.

Along with the primary end point of EFS, OS was designated as a clinically important prespecified key secondary endpoint. Other secondary end points included ORR, patient-reported outcomes, and safety.¹

Regarding safety, findings from ZUMA-7 showed that axi-cel displayed a safety profile consistent with previous studies. Among the 168 patients evaluable for safety who received axi-cel, grade 3 or higher cytokine release syndrome (CRS) was reported in 7% of patients, and neurologic events occurred in 25% of patients. In the SOC arm, 83% of patients had high-grade adverse effects, mostly consisting of cytopenias.

References

1. Kite’s Yescarta^® CAR T-cell therapy demonstrates a statistically significant improvement in overall survival for initial treatment of relapsed/refractory large B-cell lymphoma. News release. Gilead Sciences. March 21, 2023. Accessed March 21, 2023. https://investors.gilead.com/news/news-details/2023/
2. FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma. News release. FDA; April 1, 2022. Accessed March 21, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/
3. Efficacy of axicabtagene ciloleucel compared to standard of care therapy in subjects with relapsed/refractory diffuse large B cell lymphoma (ZUMA-7). ClinicalTrials.gov. Updated February 3, 2023. Accessed March 21, 2023. https://clinicaltrials.gov/ct2/show/NCT03391466