FDA 批准摘要：axicabtagene ciloleucel 用于大 B 细胞淋巴瘤二线治疗

In April 2022, the FDA approved axicabtagene ciloleucel (axi-cel) for adults with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy.

Approval was based on ZUMA-7, a randomized (1:1), open-label trial in 359 patients with primary refractory LBCL (74%) or early relapse who were transplant candidates. The study compared a single course of axi-cel to standard therapy, consisting of chemoimmunotherapy followed by high-dose therapy and autologous hematopoietic stem cell transplantation (HSCT) in responding patients.

Overall, 94% of the experimental arm received chimeric antigen receptor (CAR) T-cell product, and 35% of the control arm received on-protocol HSCT. The primary endpoint was event-free survival, which was significantly longer in the axi-cel arm with an HR of 0. 40 (95% confidence interval, 0. 31-0. 51; P value < 0. 0001) and estimated median of 8. 3 months, versus 2.

0 months with standard therapy. Among 168 recipients of axi-cel, cytokine release syndrome occurred in 92% (Grade 3, 7%), neurologic toxicity in 74% (Grade 3, 25%), prolonged cytopenias in 33%, and fatal adverse reactions in 1. 8%. This is the first FDA approval of a CAR T-cell therapy for LBCL in the second-line setting and reflects a potential paradigm shift.