Abstract
Although CD20×CD3 bispecific antibodies are effective against systemic B-cell lymphomas, their efficacy in central nervous system (CNS) lymphoma is unknown. Here, we report the CD20×CD3 bispecific glofitamab penetrates the blood-brain barrier, stimulates immune-cell infiltration of CNS tumors, and induces clinical responses in patients with secondary CNS.
References
1.
Sun
LL
, Ellerman
D
, Mathieu
M
, et al. Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies
. Sci Transl Med
. 2015
;7
(287
):287ra70
.2.
Engelberts
PJ
, Hiemstra
IH
, de Jong
B
, et al. DuoBody-CD3xCD20 induces potent T-cell-mediated killing of malignant B cells in preclinical models and provides opportunities for subcutaneous dosing
. EBioMedicine
. 2020
;52
:102625
.3.
Bacac
M
, Colombetti
S
, Herter
S
, et al. CD20-TCB with obinutuzumab pretreatment as next-generation treatment of hematologic malignancies
. Clin Cancer Res
. 2018
;24
(19
):4785
-4797
.4.
Falchi
L
, Vardhana
SA
, Salles
GA
. Bispecific antibodies for the treatment of B-cell lymphoma: promises, unknowns, and opportunities
. Blood
. 2023
;141
(5
):467
-480
.5.
Budde
LE
, Sehn
LH
, Matasar
M
, et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study
. Lancet Oncol
. 2022
;23
(8
):1055
-1065
.6.
Budde
LE
, Assouline
S
, Sehn
LH
, et al. Single-agent mosunetuzumab shows durable complete responses in patients with relapsed or refractory B-cell lymphomas: phase I dose-escalation study
. J Clin Oncol
. 2022
;40
(5
):481
-491
.7.
Dickinson
MJ
, Carlo-Stella
C
, Morschhauser
F
, et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma
. N Engl J Med
. 2022
;387
(24
):2220
-2231
.8.
Hutchings
M
, Morschhauser
F
, Iacoboni
G
, et al. Glofitamab, a novel, bivalent CD20-targeting T-cell-engaging bispecific antibody, induces durable complete remissions in relapsed or refractory B-cell lymphoma: a phase I trial
. J Clin Oncol
. 2021
;39
(18
):1959
-1970
.9.
Thieblemont
C
, Phillips
T
, Ghesquieres
H
, et al. Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-cell-engaging antibody, in relapsed or refractory large B-cell lymphoma: dose expansion in a phase I/II trial
. J Clin Oncol
. 2023
;41
(12
):2238
-2247
.10.
Schaff
LR
, Grommes
C
. Primary central nervous system lymphoma
. Blood
. 2022
;140
(9
):971
-979
.11.
Ferreri
AJM
, Doorduijn
JK
, Re
A
, et al. MATRix-RICE therapy and autologous haematopoietic stem-cell transplantation in diffuse large B-cell lymphoma with secondary CNS involvement (MARIETTA): an international, single-arm, phase 2 trial
. Lancet Haematol
. 2021
;8
(2
):e110
-e121
.12.
Rubenstein
JL
, Combs
D
, Rosenberg
J
, et al. Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment
. Blood
. 2003
;101
(2
):466
-468
.13.
Batchelor
TT
, Grossman
SA
, Mikkelsen
T
, Ye
X
, Desideri
S
, Lesser
GJ
. Rituximab monotherapy for patients with recurrent primary CNS lymphoma
. Neurology
. 2011
;76
(10
):929
-930
.14.
Herter
S
, Herting
F
, Mundigl
O
, et al. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models
. Mol Cancer Ther
. 2013
;12
(10
):2031
-2042
.15.
DeFilipp
Z
, Li
S
, El-Jawahri
A
, et al. High-dose chemotherapy with thiotepa, busulfan, and cyclophosphamide and autologous stem cell transplantation for patients with primary central nervous system lymphoma in first complete remission
. Cancer
. 2017
;123
(16
):3073
-3079
.16.
Chen
Y Bin
, Batchelor
T
, Li
S
, et al. Phase 2 trial of high-dose rituximab with high-dose cytarabine mobilization therapy and high-dose thiotepa, busulfan, and cyclophosphamide autologous stem cell transplantation in patients with central nervous system involvement by non-Hodgkin lymphoma
. Cancer
. 2015
;121
(2
):226
-233
.17.
Rubenstein
JL
, Fridlyand
J
, Abrey
L
, et al. Phase I study of intraventricular administration of rituximab in patients with recurrent CNS and intraocular lymphoma
. J Clin Oncol
. 2007
;25
(11
):1350
-1356
.© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
2024
You do not currently have access to this content.
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal