Axicabtagene Ciloleucel May Improve Long-Term Survival as Second-Line Treatment For LBCL

New long-term data suggests there may be a significant overall survival advantage for second-line treatment of relapsed/refractory large B-cell lymphoma (LBCL) with the chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (Yescarta).

Treatment with axicabtagene ciloleucel reduced the risk of mortality by 27.4% compared with standard treatment. The 4-year overall survival (OS) was 54.6% with the CAR T-cell therapy compared with 46% with standard care in the ZUMA-7 trial. The findings were published last week in the New England Journal of Medicine. Median OS was 31.1 months with standard care; median OS was not reached with axicabtagene ciloleucel.

Axicabtagene ciloleucel is “a second-line treatment option in this population on the basis of a significant improvement in survival, as opposed to a strategy of delaying cellular immunotherapy until after progression or an inadequate response to platinum-based chemotherapy,” the researchers wrote.

Axicabtagene ciloleucel is an anti-CD19 CAR T-cell therapy. This therapy involves collecting immune cells from a patient’s blood, genetically altering the cells to better target cancer cells, and then infusing the modified cells back into the patient as a one-time treatment. Axicabtagene ciloleucel targets the CD19 antigen found on the surface of B cells.

Axicabtagene is approved for the treatment of relapsed/refractory large B-cell lymphoma after two or more lines of systemic therapy and for the secondline treatment of large B-cell lymphoma relapsed/refractory.

The study included 359 patients with large B-cell lymphoma that was refractory to first-line treatment or that had relapsed within 12 months following first line treatment. Patients were randomized to receive either CAR T-cell therapy (180 patients) or standard care (179 patients). Standard care consisted of two to three cycles of chemoimmunotherapy. Patients who responded then received high-dose chemotherapy with autologous stem cell transplantation.

The researchers reported the prespecified OS analysis at 5 years post-randomization of the first patient. The primary outcome of event-free survival was previously reported. The median event-free survival was 8.3 months in the axicabtagene ciloleucel group and 2 months in the standard-care group.

In terms of safety, any grade of infection was reported in 76 patients (44.7%) in the CAR T-cell arm and in 53 (31.5%) in the standard-care group. Grade 3 or greater infections were reported in 28 patients (16.5%) and in 20 (11.9%), respectively.

B-cell aplasia (undetectable B cells) — a known complication of CAR T-cell treatment — occurred in 62.3% of the patients at 3 months and in 22.6% at 24 months after treatment infusion in the patients who were evaluated for B-cell levels at these time points. B cell aplasia can predispose patients to infection.