Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial
Mené sur 153 patients atteints d'un lymphome non hodgkinien indolent réfractaire ou récidivant, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité de l'axicabtagène ciloleucel, une immunothérapie à base de lymphocytes CAR-T ciblant CD19 (durée médiane de suivi : 17,5 mois)
Background : Most patients with advanced-stage indolent non-Hodgkin lymphoma have multiple relapses.We assessed axicabtagene ciloleucel autologous anti-CD19 chimeric antigen receptor(CAR) T-cell therapy in relapsed or refractory indolent non-Hodgkin lymphoma.
Methods : ZUMA-5 is a single-arm, multicentre, phase 2 trial being conducted at 15 medical cancercentres in the USA and two medical cancer centres in France. Patients were eligibleif they were aged 18 years or older, with histologically confirmed indolent non-Hodgkinlymphoma (follicular lymphoma or marginal zone lymphoma), had relapsed or refractorydisease, previously had two or more lines of therapy (including an anti-CD20 monoclonalantibody with an alkylating agent), and an Eastern Cooperative Oncology Group performancescore of 0 or 1. Patients underwent leukapheresis and received conditioning chemotherapy(cyclophosphamide at 500 mg/m2 per day and fludarabine at 30 mg/m2 per day on days −5, −4, and −3) followed by a single infusion of axicabtagene ciloleucel(2 × 106 CAR T cells per kg) on day 0. The primary endpoint was overall response rate (completeresponse and partial response) assessed by an independent review committee per Luganoclassification. The primary activity analysis was done after at least 80 treated patientswith follicular lymphoma had been followed up for at least 12 months after the firstresponse assessment at week 4 after infusion. The primary analyses were done in theper-protocol population (ie, eligible patients with follicular lymphoma who had 12months of follow-up after the first response assessment and eligible patients withmarginal zone lymphoma who had at least 4 weeks of follow-up after infusion of axicabtageneciloleucel). Safety analyses were done in patients who received an infusion of axicabtageneciloleucel. This study is registered with ClinicalTrials.gov, NCT03105336, and is closed to accrual.
Findings : Between June 20, 2017, and July 16, 2020, 153 patients were enrolled and underwent leukapheresis, and axicabtagene ciloleucel was successfully manufactured for all enrolledpatients. As of data cutoff (Sept 14, 2020), 148 patients had received an infusionof axicabtagene ciloleucel (124 [84%] who had follicular lymphoma and 24 [16%] whohad marginal zone lymphoma). The median follow-up for the primary analysis was 17·5months (IQR 14·1–22·6). Among patients who were eligible for the primary analysis(n=104, of whom 84 had follicular lymphoma and 20 had marginal zone lymphoma), 96(92%; 95% CI 85–97) had an overall response and 77 (74%) had a complete response.The most common grade 3 or worse adverse events were cytopenias (104 [70%] of 148patients) and infections (26 [18%]). Grade 3 or worse cytokine release syndrome occurredin ten (7%) patients and grade 3 or 4 neurological events occurred in 28 (19%) patients.Serious adverse events (any grade) occurred in 74 (50%) patients. Deaths due to adverseevents occurred in four (3%) patients, one of which was deemed to be treatment-related(multisystem organ failure).
Interpretation : Axicabtagene ciloleucel showed high rates of durable responses and had a manageablesafety profile in patients with relapsed or refractory indolent non-Hodgkin lymphoma.
The Lancet Oncology , résumé, 2020