Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial.
Level 4 - case-series / case-control
Single-arm uncontrolled phase 2 clinical trial
PubMed 34895487 · doi:10.1016/S1470-2045(21)00591-X
What was done
In a single-arm, multicentre, phase 2 trial (ZUMA-5) across 17 cancer centres in the USA and France, 153 patients with relapsed or refractory indolent non-Hodgkin lymphoma (follicular lymphoma or marginal zone lymphoma) who had received two or more prior lines of therapy were enrolled. Patients received conditioning chemotherapy (cyclophosphamide and fludarabine) followed by a single infusion of axicabtagene ciloleucel autologous anti-CD19 CAR T cells (2 × 10^6 cells/kg; n=148 treated). The primary endpoint was overall response rate (complete and partial responses) assessed by an independent review committee per Lugano classification in the per-protocol population.
What was found
Median follow-up was 17.5 months (IQR 14.1–22.6). Among 104 patients eligible for the primary efficacy analysis (84 follicular lymphoma, 20 marginal zone lymphoma), overall response rate was 92% (96/104; 95% CI 85–97) and complete response rate was 74% (77/104). Among all 148 infused patients, grade 3 or worse adverse events included cytopenias in 70% (n=104), neurological events in 19% (n=28), infections in 18% (n=26), and cytokine release syndrome in 7% (n=10). Serious adverse events occurred in 50% (n=74). Four patients (3%) died from adverse events, one deemed treatment-related.
Why it matters
Axicabtagene ciloleucel produces high overall and complete response rates in heavily pretreated relapsed or refractory indolent non-Hodgkin lymphoma, supporting CAR T-cell therapy as an active therapeutic option in this population.
Limits
The trial is single-arm and uncontrolled with no randomized comparator group. The marginal zone lymphoma cohort was small (n=24 treated, n=20 in primary analysis), and high rates of severe toxicity were reported, including grade ≥3 cytopenias in 70% and serious adverse events in 50% of patients.
Cited by
- supports CAR-T clinical trials evaluate tumor shrinkage as their primary endpoint rather than all-cause mortality.