Locke Frederick L.
CONTEXT: Axicabtagene ciloleucel (axi-cel), an anti-CD19 CAR T cell therapy, demonstrated significant clinical benefit and a manageable safety profile for patients with refractory large B cell lymphoma in ZUMA-1 (Neelapu & Locke, et al. NEJM. 2017). These results led to its approval by the US FDA for the treatment of adult patients with relapsed or refractory large B cell lymphoma after ≥ 2 prior lines of therapy. OBJECTIVE: We examined responses over time in Phase 2 of ZUMA-1. DESIGN: Patients with refractory large B cell lymphoma received 2 × 106 CAR T cells/kg after low-dose conditioning (Neelapu & Locke, et al. NEJM. 2017). Best objective response rates (BOR) were analyzed locally by investigators (local) and centrally by independent review committee (IRC; Cheson, et al. J Clin Oncol. 2007); concordance was measured as the percentage of patients whose IRC matched local. RESULTS: As of 8/11/17, median follow-up was 15.1 months for the 101 patients treated with axi-cel. While the BOR of 82% at primary analysis (median follow-up 8.7 months) by local remained consistent (83%) at long-term follow-up (median of 15.1 months), complete response (CR) rates increased from 54% to 58%. Of 34 patients with a partial response (PR) at 1 month, 11 (32%) converted to CR by the long-term follow-up. High concordance (77% – 79%) was observed for objective response rates (ORR [CR + PR]) between local and IRC at all times assessed. Landmark analysis of progression-free survival (PFS) by response status (per local) revealed that most of the 60 patients with disease control (stable disease or better) at 3 months had prolonged disease control with a 73% 12-month PFS rate. Of the 42 patients with CR and 9 with PR at 3 months, the 12-month PFS rates were 79% and 78%, respectively. CONCLUSIONS: Axi-cel induces high response rates in patients with refractory large B cell lymphoma. CR rates increased through the long-term follow-up, suggesting that responses deepen over time and that patients with PR can achieve CR as late as a year post-infusion. ORR at 3 months may be prognostic for prolonged PFS. FUNDING SOURCE: Kite, a Gilead Company
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