The chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel) demonstrated significant and clinically meaningful improvement in event-free survival (EFS) compared with second-line standard of care in patients with relapsed or refractory large B-cell lymphoma (LBCL), according to data from the ZUMA-7 trial.
Frederick L. Locke, MD, of Moffit Cancer Center in Tampa, Florida, presented results of the trial as a plenary abstract at the 2021 American Society of Hematology Annual Meeting. “The results of ZUMA-7 herald a paradigm shift in how we treat large B-cell lymphoma,” said Dr. Locke. The improvement in EFS “is remarkable and indicates that patients with lymphoma not responding to initial treatment or relapsing within 12 months should have the opportunity to get this therapy.”
Axi-cel is an autologous anti-CD19 CAR T-cell therapy that was approved by the Food and Drug Administration (FDA) for LBCL that had relapsed after or was refractory to two or more prior systemic therapies. ZUMA-7 was designed to test axi-cel as second-line treatment against standard chemoimmunotherapy.
At a median follow-up of 24.9 months, axi-cel significantly improved EFS (hazard ratio [HR] = 0.398; p < 0.0001), with a median EFS that was more than four times longer than EFS with standard of care (8.3 vs. 2.0 months). The 24-month EFS was more than twice as long (41% vs. 16%).
In addition to the improvements in EFS, overall response rates (ORR) and complete response rates (CRR) were significantly higher with axi-cel compared with standard of care. ORR was 83% with axi-cel compared with 50% with standard of care (odds ratio [OR] = 5.31; 95% CI 3.1-8.9; p < 0.0001). The CRR was more than twice as high with axi-cel (65% vs. 32%).
Median overall survival was evaluated as a preplanned interim analysis. Overall survival favored axi-cel, but it did not meet statistical significance (not reached vs. 35.1 months; HR = 0.730; p = 0.027). The researchers noted that, among patients assigned to the standard-of-care arm, 56% received commercially available or investigational CAR T-cell therapy off-protocol as a subsequent therapy.
The safety of axi-cel was manageable and consistent with third-line use, according to Dr. Locke. Most patients in both arms experienced treatment-emergent grade ≥3 adverse events (AEs). In the axi-cel arm, grade ≥3 cytokine release syndrome (CRS) occurred in 6% of patients, while grade ≥3 neurological events occurred in 21% of patients. No grade 5 CRS or neurological events occurred. “For both study arms, the rates and types of adverse events were consistent with expectations based on previous trials and real-world experience,” Dr. Locke noted.
Based on these results, Dr. Locke and colleagues suggested that axi-cel may replace chemoimmunotherapy with HCT as standard of care for second-line relapsed/refractory LBCL. “By giving CAR T-cell therapy as an earlier line of treatment, we are able to reduce the amount of chemotherapy patients are exposed to and get them quickly to a definitive therapy that can eradicate lymphoma for many years, if not forever, without a stem cell transplant,” said Dr. Locke.