ZUMA-1: Response to Axi-cel at Three Months Prognostic for Remission in B-cell Lymphoma

A long-term follow-up of the chimeric antigen receptor (CAR) T-cell treatment, axicabtagene ciloleucel (Axi-cel) in patients with B-cell lymphoma, presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, found that a response at 3 months may be prognostic for long-term remission in those patients.

An autologous anti-CD19 CAR T-cell therapy developed by Kite Pharma, Axi-cel was granted priority review following interim results that showed 82% of patients had met the primary endpoint of an objective response rate at 8.4 months of follow-up. Subsequently, the drug was approved within 5 months by the FDA for the treatment of adult patients with relapsed/refractory large B-cell lymphoma whose disease has progressed on at least 2 lines of systemic therapy.

At ASCO, Frederick Locke, MD, program coleader, Immunology, Moffitt Cancer Center and Research Institute, presented the longer-term update during an afternoon session.¹

Patients (n = 101) with refractory large B-cell lymphoma received 2 × 10⁶ CAR T cells/kg after after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine.² The best objective response rates (ORRs) were analyzed by both the local investigators and by an independent review committee (IRC).

Results collected at a median follow-up of 15.4 months showed that while the best ORR was 82% at primary analysis (median follow-up of 8.7 months), it remained consistent with a more long-term follow-up by local doctors (median 15.4 months). The complete response (CR) rates increased from 54% to 58%. Of the 34 patients who had a partial response (PR) at 3 months, 18 (44%) converted to a CR by the long-term follow-up cut off.

The researchers report observing a high concordance (77% to 79%) for ORRs between local investigators and the IRC at all times assessed.

Locke emphasized that patients who responded at 3 months had an 80% likelihood of a durable response at 12 months. Analysis of progression-free survival (PFS) by local investigators found that most of the 60 patients with disease control (stable disease or better) at 3 months had prolonged disease control and similar PFS rates over the duration:

• 6-month PFS rate was 78% PR (n = 9; range, 36-94) and 88% CR (n = 42; range 74-95)
• 9-month PFS rate was 78% PR (range 36-94) and 83% CR (range 68-92)
• 12-month PFS rate was 78% PR (range 36-94) and 79% CR (range 63-88)

The adverse events, primarily cytokine release syndrome (CRS) and neurologic events, were observed at a similar rate across all response groups, Locke said. CRS was observed in all 9 patients with PR, but all were low grade (<3); 39 CR patients experienced CRS, of which 5 were grade 3 or higher. In total, 7 PR patients experienced neurologic events, 3 of whom had grade 3 or higher events; of the 28 CR patients who had neurologic adverse events, 15 were grade 3 or higher.

The authors concluded that based on the ORR and increasing CR rates during the long-term follow-up, patients can achieve CR even 1-year out following infusion of the Axi-cel CAR T-cell treatment, which suggests that responses deepen over time.

“Patients who are in response at 3 months are 80% likely to maintain their response to the treatment at 12 months,” Locke said. He emphasized that a PR or CR at 3 months following the infusion can serve as a prognostic marker for long-term remission in patients with B-cell lymphoma administered Axi-cel.

Reference

1. Locke FL, Ghobadi A, Jacobson CA, et al. Durability of response in ZUMA-1, the pivotal phase 2 study of axicabtagene ciloleucel (Axi-Cel) in patients (Pts) with refractory large B-cell lymphoma. J Clin Oncol. 2018;36 (suppl; abstr 3003).
2. Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. doi: 10.1056/NEJMoa1707447.