Clinical trialPhase 2Lymphoma

KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma

N Engl J Med · 202074 patients enrolled; KTE-X19 was manufactured for 71 patients and infused in 68 patients

Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT, et al. N Engl J Med. 2020. 382:1331-1342

A newer report of this study has been published: Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study. (2023)

Study type: Clinical trial
Study name: ZUMA-2
Phase: Phase 2
Design: Multicentre single-arm phase 2 trial
Sample size: 74 patients enrolled; KTE-X19 was manufactured for 71 patients and infused in 68 patients
Source: N Engl J Med · 2020
Trial registration: NCT02601313

In plain words

In this study, patients with mantle cell lymphoma whose disease had come back or not improved after earlier treatments, including BTK inhibitor drugs, were treated with a single infusion of their own immune cells that had been changed in the laboratory to recognise the cancer cells (KTE-X19). Most patients responded to treatment, and in many the disease stayed in remission for a considerable time. This treatment has serious side effects, including a severe drop in blood cells, infections and nervous system side effects, and it must be given at experienced centres.

Key results

93%

Objective response (primary efficacy analysis, 60 patients)

95% CI 84 to 98

67%

Complete response (primary efficacy analysis, 60 patients)

95% CI 53 to 78

85%

Objective response (intention-to-treat analysis, 74 patients)

Complete response: 59%

57%

Patients in remission (60 patients of the primary analysis)

Median follow-up 12.3 months (range 7.0 to 32.3)

61%

Progression-free survival at 12 months (estimated)

83%

Overall survival at 12 months (estimated)

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 (single arm)

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

Source of the regimen details: Abstract of the paper; lymphodepleting regimen and dose cap from the FDA label for TECARTUS (mantle cell lymphoma)

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 who had relapsed after or were refractory to up to five prior therapies. All patients had to have received prior treatment with a BTK (Bruton's tyrosine kinase) inhibitor.

Endpoints

Primary endpoint: percentage of patients with an objective response (complete or partial response) as assessed by an independent radiological review committee according to the Lugano classification. Per protocol, the primary efficacy analysis was to be performed after 60 patients had been treated and followed for 7 months.

Safety and side effects

Common grade 3 or higher adverse events: cytopenias (in 94% of patients) and infections (in 32%). Grade 3 or higher cytokine release syndrome occurred in 15% and grade 3 or higher neurological events in 31% of patients, none of which were fatal. Two grade 5 (fatal) infectious adverse events occurred.

Clinical significance and place in guidelines

This single-arm phase 2 trial showed that CAR T therapy with KTE-X19 can produce durable remissions in patients with relapsed or refractory mantle cell lymphoma after a BTK inhibitor, who have a poor prognosis. Given the serious and life-threatening toxicities, this treatment requires well-equipped, experienced centres. The status of drug approvals and its place in clinical guidelines should be checked separately, because the abstract does not address them.

Limitations

The study was single-arm without a control group. The primary efficacy analysis was in 60 patients, and only 68 of the 74 enrolled patients received KTE-X19. Serious and life-threatening toxicities, including two deaths from infection, were reported.

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.