Axi-Cel Continues to Outperform Standard Care in Aggressive B-Cell Lymphoma

According to data from the ZUMA-7 trial, 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 standard of care in patients with relapsed or refractory large B-cell lymphoma (LBCL),

The results were presented as a plenary abstract at the 2021 American Society of Hematology Annual Meeting by Frederick L. Locke, MD, of Moffit Cancer Center in Tampa, Florida. “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.”

The US Food and Drug Administration approved axi-cel, an autologous anti-CD19 CAR T-cell therapy, for patients with LBCL that had relapsed after or was refractory to 2 or more prior systemic therapies. ZUMA-7 compared outcomes with axi-cel as second-line treatment against standard chemoimmunotherapy.

After a median follow-up of 24.9 months, axi-cel significantly improved EFS (hazard ratio [HR], .398; P < .0001), with a more than 4-fold increase in median EFS compared with standard of care (8.3 vs. 2.0 months). The 24-month EFS rate was more than doubled (41% vs. 16%).

In addition to the improvements in EFS, overall response rates (ORR) was 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, 5.31; 95% CI 3.1-8.9; P < .0001). The CRR was also more than doubled with axi-cel (65% vs. 32%).

Regarding overall survival (OS), the analysis favored axi-cel, but it did not meet statistical significance (not reached vs. 35.1 months; hazard ratio, .730; P = .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.

Dr. Locke noted that the toxicity associated with axi-cel was manageable and consistent with third-line use. Most patients in both arms experienced treatment-emergent grade ≥3 adverse events. In the axi-cel arm, grade ≥3 cytokine release syndrome (CRS) occurred in 6% of patients, while grade ≥3 neurologic events occurred in 21% of patients. No grade 5 CRS or neurologic 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 stem cell transplantation 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.

Disclosures: This research was supported by Kite, a subsidiary of Gilead. Study authors report financial relationships with Kite and Gilead, the manufacturer of axicabtagene ciloleucel.     

Reference

Locke FL, Miklos DB, Jacobson C, et al. Primary analysis of ZUMA-7: a phase 3 randomized trial of axicabtagene ciloleucel (axi-cel) versus standard-of-care therapy in patients with relapsed/refractory large B-cell lymphoma. Abstract #2. Presented at the 2021 American Society of Hematology Annual Meeting, December 12, 2021.