A phase 3 trial published in The New England Journal of Medicine has demonstrated the efficacy of axicabtagene ciloleucel (axi-cel) therapy in patients with early relapsed or refractory large B-cell lymphoma after receiving first-line chemo-immunotherapy.
Although available treatment options (chemo-immunotherapy) prognosis of patients with early relapsed or refractory large B-cell lymphoma remains poor. An international study has evaluated the efficacy of combining axicabtagene with ciloleucel.
In phase 3 international study, patients with large B-cell lymphoma that was refractory to or had relapsed no more than 12 months after first-line of chemo-immunotherapy were enrolled. Patients were randomly (1:1) administered either axicabtagene ciloleucel (axi-cel, an autologous anti-CD19 chimeric antigen receptor T-cell therapy) (n=180) or standard care (2 or 3 cycles of chemoimmunotherapy, followed by high-dose chemotherapy along with autologous stem-cell transplantation in patients with a response to the chemoimmunotherapy) (n=179). The primary endpoint of the study was event-free survival (EFS) (blinded central review), and the secondary endpoint was the response and overall survival (OS).
At a median follow-up of 24.9 months, a significant higher EFS was observed in the axi-cel group (41%) as compared to the standard-care group (16%; hazard ratio for event or death, 0.40; 95% confidence interval, 0.31 to 0.51; P<0.001). Also, more patients (83%) had responses in the axi-cel group vs standard-care (50%). An interim analysis revealed that the OS at two years was 61% and 52% in the axi-cel and standard-care groups, respectively. High levels of adverse events (grade 3 or higher) were observed in both the groups (91% of axi-cel group and 83% of standard care). However, no deaths related to cytokine release syndrome or neurologic events were reported.
Axi-cel show provides clinical benefits to patients with early relapsed or refractory large B-cell lymphoma. If approved, the combination could offer a second-line treatment option for large B-cell lymphoma patients.
Locke FL, Miklos DB, Jacobson CA, Perales MA, et al. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2021 Dec 11. doi: 10.1056/NEJMoa2116133. Epub ahead of print. PMID: 34891224.