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