Prescribing Information

Home / Efficacy / ZUMA-2 Pivotal Trial

In patients with relapsed or refractory (R/R) mantle cell lymphoma

The ZUMA-2 trial was the pivotal, phase 2 clinical study for TECARTUS1,2

ZUMA-2 was a phase 2, multicenter, international, single-arm, open-label clinical study1,2

74 previously treated
patients with
R/R MCL
enrolled and leukapheresed1

Conditioning treatment of
fludarabine
and
cyclophosphamide (n=69)2,3*

One IV infusion of
autologous
CAR T-cell
therapy (n=68)1†

Primary efficacy
endpoint:
ORR1

Selected secondary
endpoints:
DOR,
PFS, safety2

  • 60 of the 68 patients who were infused were followed for at least 6 months after their first objective disease response and were evaluable in the efficacy analysis1‡
  • Bridging therapy between leukapheresis and lymphodepleting chemotherapy was permitted to control disease burden1,2

Key inclusion criteria2,3

  • One to 5 prior regimens for MCL. Prior therapy must have included all of the following:
    • Anthracycline- or bendamustine-containing chemotherapy
    • Anti-CD20 monoclonal antibody therapy
    • BTKi (ibrutinib or acalabrutinib)
  • At least 1 measurable lesion
  • Age ≥18 years
  • ECOG PS 0 or 1
  • Adequate bone marrow, renal, hepatic, pulmonary, and cardiac functions
  • ALC ≥100 cells/mm3

Key exclusion criteria1,3

  • Previously received allogeneic HSCT, CD19-targeted therapy, or CAR T-cell therapy
  • History of HIV infection or acute or chronic active hepatitis B or C infection. Patients with a history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing
  • History or presence of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with CNS involvement
  • Presence of fungal, bacterial, viral, or other infection that was uncontrolled or required IV antimicrobials for management

*Consisted of cyclophosphamide 500 mg/m2 intravenously and fludarabine 30 mg/m2 intravenously, both given on the fifth, fourth, and third day before TECARTUS.1
†TECARTUS was administered to patients as a single intravenous infusion at a dose of 2 × 106 anti-CD19 CAR T cells/kg (maximum permitted dose:
2 × 108 cells).1
‡Among the 60 efficacy-evaluable patients, 2 x 106 CAR-positive viable T cells/kg were administered to 54 patients (90%). The remaining 6 patients (10%) received doses of 1.0, 1.6, 1.8, 1.8, 1.9, and 1.9 x 106 CAR-positive viable T cells/kg.1

TECARTUS was studied in a range of patients with R/R MCL—a historically difficult-to-treat population1,4,5

Baseline patient
characteristics in all
treated patients (n=68)2,3§

Age, median
(range), years

65
(38–79)

Male

84%

ECOG PS

0

1

 

65%

35%

Patients with
extranodal disease

56%

Patients with bone
marrow involvement

54%

Intermediate/high-risk
simplified MIPI

56%

Patients with high-risk
characteristics

Blastoid/pleomorphic
MCL morphology

TP53 mutation  

Ki-67 proliferation
index ≥30%

  

31%  

17%
(n=6/36)

82%
(n=40/49)

Prior autologous SCT

43%

Positive CD19 status

92%
(n=47/51)

Number of prior
therapies, median
(range)

3 (range:
1–5)

Prior BTKi therapy

Ibrutinib

Acalabrutinib

Both

100%

85%

24%

9%

Relapsed/refractory
subgroup

Relapsed after
autologous SCT

Refractory to last
prior therapy

Relapsed after
last prior therapy

  

43% 

40% 

18%

BTKi relapsed/
refractory status

Refractory to BTKi

Relapsed on BTKi

Relapsed after BTKi

Intolerant to BTKi

  

62%

26%

7%

4%

§These data are based on all treated patients (n=68); USPI reports patient characteristics in efficacy-evaluable patients (n=60).1,2

Patients with high-risk characteristics were enrolled in the registration trial, including patients with blastoid
morphology, TP53 mutation, or Ki-67 index ≥30%2

ALC=absolute lymphocyte count; BTKi=Bruton’s tyrosine kinase inhibitor; CAR=chimeric antigen receptor; CD=cluster of differentiation; CNS=central nervous system; DOR=duration of response; ECOG=Eastern Cooperative Oncology Group; HIV=human immunodeficiency virus; HSCT=hematopoietic stem cell transplant; IV=intravenous; MCL=mantle cell lymphoma; MIPI=Mantle Cell Lymphoma International Prognostic Index; ORR=objective response rate; PFS=progression-free survival; PS=performance status; R/R=relapsed or refractory; SCT=stem-cell transplant; USPI=US Prescribing Information.

References: 1. TECARTUS® (brexucabtagene autoleucel). Prescribing information. Kite Pharma, Inc; 2021. 2. Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-cell therapy in relapsed or refractory mantle cell lymphoma. N Engl J Med. 2020;382(14):1331-1342. 3. Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-cell therapy in relapsed or refractory mantle cell lymphoma - supplementary appendix. N Engl J Med. 2020;1-33. 4. Martin P, Maddocks K, Leonard JP, et al. Postibrutinib outcomes in patients with mantle cell lymphoma. Blood. 2016;127(12):1559-1563. 5. Dreyling M, Klapper W, Rule S. Blastoid and pleomorphic mantle cell lymphoma: still a diagnostic and therapeutic challenge! Blood. 2018;132(26):2722-2729.

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