Anti-CD19 CAR T-cell therapy in relapsed/refractory indolent NHL

Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimaeric antigen receptor (CAR) T cell therapy approved for the treatment of relapsed or refractory (R/R) large B-cell lymphoma (LBCL) after ≥2 lines of systemic therapy, demonstrated considerable and durable clinical benefit in patients with R/R indolent non-Hodgkin lymphoma (iNHL) [1]. Axi-cel had a manageable safety profile, with lower rates of grade ≥3 neurologic events observed in patients with follicular lymphoma compared with patients with marginal zone lymphoma and with aggressive NHL [2].

Patients with advanced-stage iNHL, including follicular lymphoma and marginal zone lymphoma, frequently relapse with standard treatment. Axi-cel had positive results in relapsed LBCL [3] and is therefore investigated as potential therapy in iNHL. Dr Caron Jacobson (Dana Farber Cancer Institute, Massachusetts, USA) presented the primary analysis of ZUMA-5 (NCT03105336), a multicentre, single-arm, phase 2 study of axi-cel in patients with R/R iNHL after ≥2 lines of therapy [1].

Axi-cel resulted in high rates of durable responses, with an overall response rate of 92% in patients with iNHL (94% in follicular lymphoma) and a complete response rate of 76% (80% in follicular lymphoma). “Although longer follow-up is needed, these responses appeared to be durable,” Dr Jacobson said. Response rates were consistent among patients with high-risk features. With a median follow-up of 17.5 months, 64% of patients with follicular lymphoma remained in response and responses were ongoing in 78% of patients who achieved a complete response.

The safety profile was manageable and appeared favourable in patients with follicular lymphoma, consistent with that previously reported in LBCL [4]. A lower incidence of grade ≥3 neurologic events was observed in patients with follicular lymphoma compared with marginal zone lymphoma. No grade 5 neurologic events occurred; one event of grade 5 cytokine-release syndrome occurred [1]. Based on the safety profile observed, an evaluation of the potential for outpatient treatment with axi-cel in iNHL is planned.

1. Jacobson C, et al. Primary Analysis of Zuma-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL). 62^nd ASH Annual Meeting, 5-8 December 2020. Abstract 700.
2. Locke FL, et al. Lancet Oncol. 2019;20:31-42.
3. Jacobson C, et al. Long-Term Survival and Gradual Recovery of B Cells in Patients with Refractory Large B Cell Lymphoma Treated with Axicabtagene Ciloleucel (Axi-Cel). 62^nd ASH Annual Meeting, 5-8 December 2020. Abstract 1187.
4. Neelapu SS, et al. N Engl J Med. 2017;377:2531-44.

 



Posted on 18 February 202119 November 2021