In this study, patients with large B-cell lymphoma that had come back early or had not responded to the first treatment were randomly assigned to either CAR-T cell therapy (axicabtagene ciloleucel) or standard treatment (chemotherapy and, if it worked, a transplant of the patient's own stem cells). After about four years of follow-up, patients who had CAR-T therapy lived meaningfully longer. CAR-T therapy also kept the disease from growing for longer. Since the first analysis, no new treatment-related deaths had been reported.
Key results
47.2 months
Median follow-up
82 patients in the axicabtagene ciloleucel group vs 95 patients in the standard-care group
Number of deaths
Not reached vs 31.1 months
Median overall survival
Axicabtagene ciloleucel vs standard care
54.6% vs 46.0%
Estimated 4-year overall survival
Hazard ratio for death 0.73; 95% CI 0.54 to 0.98; P=0.03
14.7 months vs 3.7 months
Median progression-free survival (investigator assessment)
Large B-cell lymphoma refractory to first-line therapy or relapsed within 12 months of first-line therapy; or after 2 or more lines of therapyCycle length: One-timeOn the page “Blood cancers (leukaemia, lymphoma and myeloma)” · Treatment regimens and dosing in lymphomas
Large B-cell lymphoma refractory to first-line therapy or relapsed within 12 months of first-line therapy; or after 2 or more lines of therapy
Second-line CAR T-cell therapy: axicabtagene ciloleucel (ZUMA-7) or lisocabtagene maraleucel (TRANSFORM)
Large B-cell lymphoma refractory to first-line treatment or relapsing within 12 months of it (candidates for intensive therapy)Cycle length: Single doseOn the page “Lymphoma” · Treatment regimens and dosing: relapsed or refractory DLBCL, eligible for transplantation or CAR T-cell therapy
Large B-cell lymphoma refractory to first-line treatment or relapsing within 12 months of it (candidates for intensive therapy)
Once, 2 to 7 days after completion of lymphodepletion
Cycle length
Single dose
Duration
One-time infusion
Doses from the FDA labels for YESCARTA and BREYANZI. Before infusion, acetaminophen and an H1 antihistamine; tocilizumab and emergency equipment must be available; the patient should stay near the treatment centre for at least 2 weeks after axi-cel infusion. In ZUMA-7, grade 3 or higher cytokine release syndrome occurred in 6% and grade 3 or higher neurologic events in 21% of patients. In renal impairment, adjust the fludarabine and cyclophosphamide doses according to the labels of these drugs.
On the fifth, fourth and third days before the CAR-T infusion
Fludarabine
30 mg/m² daily
IV
On the fifth, fourth and third days before the CAR-T infusion
Cycle length
Once
Duration
3 days (day 0: cell infusion)
Doses and days as per the FDA label for axicabtagene ciloleucel (Yescarta) and the ZUMA-7 trial. Before starting lymphodepletion, make sure the patient's CAR-T product is available.
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Treatment arms and regimens
1Axicabtagene ciloleucel (axi-cel)
Lymphodepleting chemotherapy with 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 viable CAR-positive T cells per kg (maximum 2 × 108 cells) on day 0.
2Standard care
Two or three 21-day cycles of investigator-selected salvage chemoimmunotherapy (R-ICE, R-ESHAP, R-GDP or R-DHAP at protocol-defined doses) and, in responders, high-dose chemotherapy with autologous stem-cell transplantation.
Source of the regimen details: ClinicalTrials.gov NCT03391466 and the FDA label for YESCARTA (Dosage and Administration section)
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 early relapsed or refractory large B-cell lymphoma. According to the abstract, 74% of patients had primary refractory disease and other high-risk features.
Endpoints
Primary endpoint: event-free survival. Key secondary endpoints: response and overall survival. This report presents the results of the prespecified overall survival analysis at 5 years after randomisation of the first patient.
Safety and side effects
According to the abstract, no new treatment-related deaths had occurred since the primary event-free survival analysis. In the primary ZUMA-7 report, grade 3 or higher adverse events occurred in 91% of the axi-cel group and 83% of the standard-care group; grade 3 or higher cytokine release syndrome in 6% and grade 3 or higher neurological events in 21% of the axi-cel group.
Clinical significance and place in guidelines
This analysis shows that axicabtagene ciloleucel as second-line therapy in early relapsed or refractory large B-cell lymphoma improves not only event-free survival but also overall survival compared with standard care (chemoimmunotherapy and autologous transplantation). The results were obtained in a population in which 74% had primary refractory disease and high-risk features. The exact status of regulatory approvals and guideline recommendations should be checked separately, because they are not reported in the abstract.
Limitations
The abstract does not address rates of grade 3 or higher adverse events or safety details (such as cytokine release syndrome or neurological events). Dose and schedule details are also not in the abstract and should be checked in the full text. Progression-free survival was reported by investigator assessment. The trial was funded by Kite.
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.
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