The FDA has approved axicabtagene ciloleucel (axi-cel) for the treatment of adult patients with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. This approval marks a significant advancement in the treatment landscape for LBCL, offering a new option for patients who have not responded to initial treatment. The decision was based on the pivotal ZUMA-7 trial, a randomized, open-label study involving 359 patients.
ZUMA-7 Trial Results
The ZUMA-7 trial compared a single course of axi-cel to standard therapy, which consisted of chemoimmunotherapy followed by high-dose therapy and autologous hematopoietic stem cell transplantation (HSCT) in responding patients. The study population included patients with primary refractory LBCL (74%) or early relapse who were transplant candidates. In the experimental arm, 94% of patients received the CAR T-cell product, while 35% of the control arm underwent on-protocol HSCT.
The primary endpoint of event-free survival was significantly longer in the axi-cel arm, with a hazard ratio of 0.40 (95% confidence interval, 0.31-0.51; P value < 0.0001). The estimated median event-free survival was 8.3 months in the axi-cel arm compared to 2.0 months with standard therapy. This statistically significant and clinically meaningful improvement underscores the potential of axi-cel to alter the treatment paradigm for second-line LBCL.
Safety Profile
While axi-cel demonstrated significant efficacy, it is associated with notable adverse events. Among the 168 recipients of axi-cel, cytokine release syndrome occurred in 92% of patients, with Grade ≥ 3 severity in 7%. Neurologic toxicity was observed in 74% of patients, with Grade ≥ 3 severity in 25%. Prolonged cytopenias were reported in 33% of patients, and fatal adverse reactions occurred in 1.8%. These findings emphasize the importance of careful patient selection and monitoring during and after axi-cel treatment.
Implications for LBCL Treatment
This FDA approval represents the first CAR T-cell therapy approved for LBCL in the second-line setting. The results of the ZUMA-7 trial suggest that axi-cel could become a new standard of care for patients with relapsed or refractory LBCL, potentially improving outcomes compared to traditional chemoimmunotherapy and stem cell transplantation. However, the risk of significant toxicities requires careful consideration and management.
