Clinical trialLymphoma

Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study.

J Clin Oncol · 202368 treated patients

Wang M, Munoz J, Goy A, et al. J Clin Oncol. 2023. 41:555-567

Study type: Clinical trial
Study name: ZUMA-2
Design: Single-arm trial; 3-year follow-up report (median follow-up 35.6 months) with post hoc subgroup analyses and exploratory and translational analyses
Sample size: 68 treated patients
Source: J Clin Oncol · 2023
Trial registration: NCT02601313

In plain words

This report gives the results of about three years of follow-up of 68 patients with mantle cell lymphoma whose disease had come back or resisted earlier treatments, including BTK inhibitor drugs, and who received a single infusion of their own immune cells changed in the laboratory to recognise the lymphoma cells (CAR T). More than 9 in 10 patients responded and about two thirds had a complete response. Half of the patients lived at least about 4 years, and late side effects were rare. This treatment also seemed to work in high-risk patients.

Key results

91%

Objective response rate

95% CI 81.8 to 96.7; in 68 treated patients; median follow-up 35.6 months

68%

Complete response

95% CI 55.2 to 78.5

28.2 months

Median duration of response

95% CI 13.5 to 47.1

25.8 months

Median progression-free survival

95% CI 9.6 to 47.6

46.6 months

Median overall survival

95% CI 24.9 to not estimable

Drugs in this study:Cyclophosphamide (Endoxan)

Dose and schedule cards

Brexucabtagene autoleucel (CAR T-cell therapy; ZUMA-2 trial)

Relapsed or refractory mantle cell lymphoma, including after failure of a BTK inhibitorCycle length: Single doseOn the page “Lymphoma” · Treatment regimens and dosing: mantle cell lymphoma

Relapsed or refractory mantle cell lymphoma, including after failure of a BTK inhibitor

Drug	Dose	Route	Schedule
Lymphodepletion
Cyclophosphamide	500 mg/m²	IV	Days −5, −4 and −3 before infusion
Fludarabine	30 mg/m²	IV	Days −5, −4 and −3 before infusion
Brexucabtagene autoleucel	2 × 10⁶ CAR-positive viable T cells/kg (maximum 2 × 10⁸ cells)	IV	Once, Day 0

Cycle length: Single dose
Duration: One-time infusion

Doses from the FDA label for TECARTUS; results from ZUMA-2. Monitoring for cytokine release syndrome and neurologic toxicities as with other CAR T-cell products.

On the page “Lymphoma” · Treatment regimens and dosing: mantle cell lymphoma

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

1KTE-X19 (brexucabtagene autoleucel)

Lymphodepleting chemotherapy with cyclophosphamide 500 mg/m² and fludarabine 30 mg/m² IV on days -5, -4 and -3, followed by a single infusion of brexucabtagene autoleucel (KTE-X19), an autologous anti-CD19 CAR T-cell therapy, at a dose of 2 × 10⁶ CAR T cells per kg (maximum 2 × 10⁸).

Source of the regimen details: Abstract of the paper on PubMed; lymphodepleting regimen from the FDA label for TECARTUS

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 relapsed or refractory mantle cell lymphoma (MCL) after one to five prior therapies, all of whom had previously received a Bruton's tyrosine kinase inhibitor (BTKi).

Endpoints

Objective response rate, complete response, duration of response, progression-free survival, overall survival and safety; plus subgroup analyses by prior therapy (bendamustine and type of BTKi) and high-risk features.

Safety and side effects

Late toxicities were rare; only 3% of treatment-emergent adverse events of interest in ZUMA-2 occurred during this longer follow-up period.

Clinical significance and place in guidelines

This 3-year follow-up confirms the durability of responses to KTE-X19 in relapsed or refractory MCL after a BTKi and shows that responses are also seen in high-risk subgroups. The exploratory finding on recent bendamustine (before leukapheresis) and possibly reduced T-cell fitness may be considered when planning treatment sequencing, but requires confirmation.

Limitations

Single-arm study without a control group and with a limited number of patients (68). The subgroup analyses are post hoc, and the bendamustine analysis and translational assessments are exploratory.

Original article (DOI)PubMed ClinicalTrials.gov

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.