Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma
- Study type
- Clinical trial
- Study name
- ZUMA-1
- Phase
- Phase 2
- Design
- Multicentre phase 2 trial
- Sample size
- 111 patients enrolled; axi-cel was successfully manufactured for 110 patients (99%) and 101 patients (91%) received it
- Source
- N Engl J Med · 2017
- Trial registration
- NCT02348216
In plain words
In this study, patients with a type of large B-cell lymphoma that had not responded to earlier treatments were treated with their own immune cells. These cells had been changed in the laboratory to recognise and attack the cancer cells (CAR T therapy). About 82% of patients responded to treatment, and in 54% the cancer disappeared completely. This treatment also had serious side effects, including a severe drop in blood cells, a strong inflammatory reaction (cytokine release syndrome) and nervous system side effects, and it must be given at specialist centres.
Key results
Treatment arms and regimens
Lymphodepleting regimen of cyclophosphamide 500 mg/m² and fludarabine 30 mg/m² IV on days -5, -4 and -3 before infusion, followed by a single infusion of axicabtagene ciloleucel at a target dose of 2 × 106 anti-CD19 CAR-positive T cells per kg.
Source of the regimen details: Abstract of the paper; lymphodepleting regimen dose from the FDA label for YESCARTA (Clinical Studies section, ZUMA-1)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma or transformed follicular lymphoma who had refractory disease despite receiving the recommended prior therapy.
Endpoints
Primary endpoint: objective response rate (combined rates of complete and partial response). Secondary endpoints: overall survival, safety and biomarker assessments.
Safety and side effects
The most common grade 3 or higher adverse events during treatment: neutropenia (78% of patients), anaemia (43%) and thrombocytopenia (38%). Grade 3 or higher cytokine release syndrome occurred in 13% and grade 3 or higher neurological events in 28% of patients. Three patients died during treatment. Higher blood levels of CAR T cells were associated with response.
Clinical significance and place in guidelines
This study showed that anti-CD19 CAR T therapy with axi-cel can produce high and durable responses in refractory large B-cell lymphoma. According to the abstract, treatment is associated with adverse events such as myelosuppression, cytokine release syndrome and neurological events. The status of drug approvals and the place of this treatment in current clinical guidelines should be checked separately.
Limitations
According to the abstract, this was a phase 2 trial and no control group is mentioned. Median follow-up was 15.4 months. 10 of the 111 enrolled patients did not receive axi-cel. Three deaths during treatment were reported and grade 3 or higher adverse events were common. The study was funded by Kite Pharma.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.