On Saturday 2nd June, an oral abstract session took place at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting. Abstract 3003 was presented by Frederick Locke, Moffitt Cancer Center, Florida, on the durability of response of axicabtagene ciloleucel (Axi-Cel) in the ZUMA-1 phase II study.
Axi-Cel, also known as YESCARTA, was approved for the treatment of relapsed/refractory (R/R) adult B-cell lymphomas including diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL) and transformed follicular lymphoma (TFL) by the US Food and Drug Administration on 18th October 2017. At the interim and primary analyses of ZUMA-1, Axi-Cel met its primary endpoint that led to its approval in the US.
The results presented at ASCO represented the duration of response at a median follow-up of 15.4 months in 108 large B-cell lymphoma patients treated with Axi-Cel. The median duration of response was 11.1 months (95% CI, 3.9–not reached [NR]). The overall response rate was 82% with a complete response (CR) rate of 58%. The median overall survival was not reached. Additionally, at 3 months, progression-free survival for patients with CR and partial response (PR) was not reached.
Dr. Locke highlighted that patients who were responding at 3 months had almost 80% chance of maintaining a response at 1 year. He noted that, “the three-month time point is an important disease response time point.” In an interview with Lymphoma Hub, Dr. Locke commented further on the study results, saying that the responses were “remarkable” and, “even patients with a partial response, many of those responses deepened over time and some of the patients converted from a partial response to a complete response as late as 1 year after the therapy.” He advised that additional therapy should not be recommended for patients who have had a response to CAR-T therapy.
The rates of cytokine release syndrome (CRS) and neurotoxicity were similar across all response groups in this study. Dr. Locke noted that earlier intervention with tocilizumab or corticosteroids could lower rates of grade ≥ 3 CRS or neurologic events.
He concluded that durable responses were seen with treatment with Axi-Cel and high response rates for patients with refractory large B-cell lymphoma. Additionally, responses at 3 months could be prognostic for long-term remission.
Locke F., 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. Journal of Clinical Oncology 36, 2018 (suppl; abstr 3003) . 2018 ASCO Annual Meeting, Chicago, Illinois.