The long-term overall survival rate achieved by the axicabtagen ciloleucel appeared to support event-free survival at 1 and 2 years as a surrogate endpoint in relapsed/refractory large B-cell lymphoma.

Long-term overall survival (OS) results from the Phase 2 ZUMA-1 trial (NCT02348216) appear to support the 1- and 2-year event-free survival (EFS) results of axicabtagene ciloleucel (axi-cel; Yescarta) in patients with relapsed/refractory large B-cell lymphoma (LBCL), based on data presented at Tandem Meeting 2022.

Investigators reported a 5-year OS rate of 42.6% (95% CI, 32.8% to 51.9%) after treatment with axi-cel. In the complete responder patient population, the 5-year OS rate was 64.4% (95% CI 50.8% to 75.1%) and the median OS was not achieved (95% CI, 63.4% – not estimated). Additionally, 63% of complete responders were alive at the 5-year data cutoff. At the 4-year data cutoff, 1 patient died at month 63 and 1 patient had disease progression at month 54.

The 5-year OS rates among those with or without an SES event at month 12 were 5.3% (95% CI, 1.4% to 13.2%) versus 90, 9% (95% CI, 77.6% to 96.5%), respectively. Median OS was 8.3 months in those who experienced an event and median OS was not reached in those who did not experience an event. Additionally, the 5-year OS rates among those with or without an SES event at month 24 were 11.3% (95% CI, 5.0% to 20.5% ) and 92.3% (95% CI, 78.0% to 97.5%) respectively. Moreover, the median OS in the two respective groups was 9.2 months and was not achieved.

“In this updated 5-year analysis, axi-cel-induced long-term OS…among treated patients,” says Caron A. Jacobson, MD, MMSc, ​​Cell Therapy Program Medical Director immune effector and senior physician at Dana-Farber Cancer Institute and assistant professor of medicine at Harvard Medical School. She continued: “Between the analysis at 4 and 5 years, the time to next treatment curve remains stable and 92% of the patients remained alive without the need for further treatment, which may suggest a cure. in these patients.

To be considered for treatment, patients had to have refractory LBCL, including diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma. Patients also had to be unresponsive to their last chemotherapy or relapse 12 months or less after autologous stem cell transplantation. Prior treatment with an anti-CD20 monoclonal antibody and an anthracycline was also necessary.

Those who completed treatment received a conditioning regimen of cyclophosphamide 500 mg/m2 and 30 mg/m2 of fludarabine for 3 days. This was followed by axi-cel at a dose of 2×106 CAR T cells/kg. The primary endpoint was the overall response rate with an initial assessment of response 4 weeks after infusion. Primary secondary endpoints included assessments of OS, safety, and translation.

A total of 111 patients were included in the study, 8 of whom did not receive treatment due to adverse effects (AE; n = 4), no measurable disease (n = 2), death due to disease progression (n=1), and manufacturing defect (n=1); this left 103 patients to undergo conditioning. Of these patients, 2 were not treated due to AE and death, respectively. One hundred and one patients were infused. The data cutoff date was August 11, 2021, and the median follow-up was 63.1 months.

Other trial results showed a median time to next cancer treatment of 8.7 months after the infusion. A total of 34% of patients were alive at the cut-off date without further treatment or retreatment with axi-cel. Two patients who had prior progression received new cancer treatment.

An exploratory analysis revealed among all treated patients that the rate of SSE at 12 months was 42.8% (95% CI, 33.0%-52.3%) and the rate of SSE at 24 months was 37.7% (95% CI, 28.3%-47.2%) .

The researchers also determined that early expansion of CAR T cells was associated with a continued response at 60 months. Median peaks in CAR T levels appeared to be numerically higher in those who had a continuous response at month 60 and lower in those who relapsed or did not respond to treatment. Similarly, another trend was observed in those who experienced an expansion of CAR T cells by area under the curve from day 0 to day 28.

A total of 58% of patients had died by the cut-off date. No new safety signals were observed at the 5-year data cutoff, including serious AEs or treatment-related secondary malignancies. Patients most often died due to progressive disease (n=45), IE (n=4), secondary malignancies (n=1), or other reasons (n=9) .

Reference

Jacobson C, Locke FL, Ghobadi A, et al. Long-term overall survival (5 years) in Zuma-1, the pivotal study of axicabtagene ciloleucel in patients with refractory large B-cell lymphoma. Presented at: 2022 Tandem Meeting; April 23-26, 2022; Salt Lake City, UT. Summary 10.