• Bispecifics had an ORR and CR rate of 51.7% and 25.4%, respectively; median PFS and OS were 2.5 and 7.8 months, respectively.

  • Undetectable CD20 at baseline is associated with poor prognosis; consider assessing CD20 in biopsies before therapy and in nonresponders.

Abstract

Epcoritamab and glofitamab are CD20-directed bispecific antibodies (BsAbs) approved in the United States for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Limited data exist for patients treated outside of trials. Patients with R/R DLBCL receiving commercial epcoritamab or glofitamab between 1 January 2023 and 15 October 2024 were collected from 21 United States institutions. Among 245 patients, 156 received epcoritamab and 89 received glofitamab, 113 were refractory to front-line therapy, 40 had MYC and BCL2 and/or BCL6 rearrangements, 147 received prior chimeric antigen receptor T-cell therapy, and 174 patients would have been ineligible for registrational trials. The overall response rate (ORR) for epcoritamab and glofitamab was 51% (23% complete response, [CR]) and 53% (30% CR), respectively. Median progression-free survival (PFS) was 2.6 months (95% confidence interval [CI], 2.0-3.8 months), and median overall survival (OS) was 7.8 months (95% CI, 6.2-11.0 months). The 6-month PFS was 36% (95% CI, 30-44) and the 6-month OS was 60% (95% CI, 54-67). Both trial ineligibility and undetectable CD20 pre-BsAbs portended shorter PFS and OS. Of 17 individuals with paired biopsies, 15 (88.2%) lost CD20 expression after BsAbs with a median time to progression of 3.7 months. This analysis including patients with R/R DLBCL shows the ORR to CD3/CD20 BsAbs was comparable to pivotal trials, although PFS and OS were lower. Baseline undetectable levels of CD20 were associated with poor outcomes. These results demonstrate the activity of BsAbs in R/R DLBCL, and underscore the importance of target antigen expression.

1.
Alencar
AJ
,
Moskowitz
CH
.
Autologous stem cell transplantation in the management of relapsed non-Hodgkin lymphoma
.
J Clin Oncol
.
2021
;
39
(
5
):
467
-
475
.
2.
Morrison
VA
,
Shou
Y
,
Bell
JA
, et al
.
Evaluation of treatment patterns and survival among patients with diffuse large B-cell lymphoma in the USA
.
Future Oncol
.
2019
;
15
(
9
):
1021
-
1034
.
3.
Tun
AM
,
Wang
Y
,
Maliske
S
, et al
.
Autologous stem cell transplant in fit patients with late relapsed diffuse large B-cell lymphoma that responded to salvage chemotherapy
.
Transpl Cell Ther
.
2024
;
30
(
10
):
1001.e1
-
1001.e12
.
4.
Tun
AM
,
Maliske
S
,
Wang
Y
, et al
.
Progression-free survival at 24 months as a landmark after autologous stem cell transplant in relapsed or refractory diffuse large B-cell lymphoma
.
Transpl Cell Ther
.
2022
;
28
(
9
):
610
-
617
.
5.
Fox
CP
,
Townsend
W
,
Gribben
JG
, et al
.
Real-world outcomes of patients with relapsed/refractory large B-cell lymphoma receiving second-line therapy in England
.
EJHaem
.
2024
;
5
(
5
):
992
-
997
.
6.
Abramson
JS
,
Palomba
ML
,
Gordon
LI
, et al
.
Two-year follow-up of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma in TRANSCEND NHL 001
.
Blood
.
2024
;
143
(
5
):
404
-
416
.
7.
Westin
JR
,
Oluwole
OO
,
Kersten
MJ
, et al
.
Survival with axicabtagene ciloleucel in large B-cell lymphoma
.
N Engl J Med
.
2023
;
389
(
2
):
148
-
157
.
8.
Sehgal
A
,
Hoda
D
,
Riedell
PA
, et al
.
Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study
.
Lancet Oncol
.
2022
;
23
(
8
):
1066
-
1077
.
9.
Abramson
JS
,
Solomon
SR
,
Arnason
J
, et al
.
Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study
.
Blood
.
2023
;
141
(
14
):
1675
-
1684
.
10.
Jain
MD
,
Spiegel
JY
,
Nastoupil
LJ
, et al
.
Five-year follow-up of standard-of-care axicabtagene ciloleucel for large B-cell lymphoma: results from the US Lymphoma CAR T Consortium
.
J Clin Oncol
.
2024
;
42
(
30
):
3581
-
3592
.
11.
Sehn
LH
,
Herrera
AF
,
Flowers
CR
, et al
.
Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma
.
J Clin Oncol
.
2020
;
38
(
2
):
155
-
165
.
12.
Caimi
PF
,
Ai
W
,
Alderuccio
JP
, et al
.
Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial
.
Lancet Oncol
.
2021
;
22
(
6
):
790
-
800
.
13.
Salles
G
,
Duell
J
,
González Barca
E
, et al
.
Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study
.
Lancet Oncol
.
2020
;
21
(
7
):
978
-
988
.
14.
Kalakonda
N
,
Maerevoet
M
,
Cavallo
F
, et al
.
Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial
.
Lancet Haematol
.
2020
;
7
(
7
):
e511
-
e522
.
15.
Jacobsen
ED
,
Sharman
JP
,
Oi
Y
, et al
.
Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression
.
Blood
.
2015
;
125
(
9
):
1394
-
1402
.
16.
Thieblemont
C
,
Karimi
YH
,
Ghesquieres
H
, et al
.
Epcoritamab in relapsed/refractory large B-cell lymphoma: 2-year follow-up from the pivotal EPCORE NHL-1 trial
.
Leukemia
.
2024
;
38
(
12
):
2653
-
2662
.
17.
Thieblemont
C
,
Phillips
T
,
Ghesquieres
H
, et al
.
Epcoritamab, a novel, subcutaneous CD3×CD20 bispecific T-cell-engaging antibody relapsed or refractory large B-cell lymphoma: dose expansion in a phase I/II trial
.
J Clin Oncol
.
2023
;
41
(
12
):
2238
-
2247
.
18.
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
.
19.
Hans
CP
,
Weisenburger
DD
,
Greiner
TC
, et al
.
Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray
.
Blood
.
2004
;
103
(
1
):
275
-
282
.
20.
Cheson
BD
,
Fisher
RI
,
Barrington
SF
, et al
.
Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification
.
J Clin Oncol
.
2014
;
32
(
27
):
3059
-
3068
.
21.
Landsburg
DJ
,
Morrissette
JJ
,
Nasta
SD
, et al
.
TP53 mutations predict for poor outcomes in patients with newly diagnosed aggressive B-cell lymphomas in the current era
.
Blood Adv
.
2023
;
7
(
23
):
7243
-
7253
.
22.
Iacoboni
G
,
Navarro
V
,
Martín-López
, et al
.
Recent bendamustine treatment before apheresis has a negative impact on outcomes in patients with large B-cell lymphoma receiving chimeric antigen receptor T-cell therapy
.
J Clin Oncol Off J Am Soc Clin Oncol
.
2024
;
42
(
2
):
205
-
217
.
23.
Iacoboni
G
,
Iraola-Truchuelo
J
,
O’Reilly
M
, et al
.
Treatment outcomes in patients with large B-cell lymphoma after progression to chimeric antigen receptor T-cell therapy
.
Hemasphere
.
2024
;
8
(
5
):
e62
.
24.
Iacobon
G
,
Navarro
V
,
Sesques
P
, et al
.
Development and validation of the post-CAR prognostic index for large B-cell lymphoma patients after CAR-T progression in third or later line treatment
.
J Hematol Oncol
.
2024
;
17
(
1
):
102
.
25.
Yan
Z
,
Zhang
H
,
Cao
J
, et al
.
Characteristics and risk factors of cytokine release syndrome in chimeric antigen receptor T cell treatment
.
Front Immunol
.
2021
;
12
:
611366
.
26.
Yang
X
,
Ahmed
I
,
Nachar
V
, et al
.
Risk factors for cytokine release syndrome in patients receiving bispecific antibodies for B-cell lymphoma: a single-center, retrospective cohort study [abstract]
.
Blood
.
2024
;
144
(
suppl 1
):
4477
.
27.
Gritti
G
,
Belousov
A
,
Relf
J
,
Dixon
M
,
Tandon
M
,
Komanduri
K
.
Predictive model for the risk of cytokine release syndrome with glofitamab treatment for diffuse large B-cell lymphoma
.
Blood Adv
.
2024
;
8
(
14
):
3615
-
3618
.
28.
Carlo-Stella
C
.
Relapse after glofitamab, a novel unmet medical need with high rates of CD20 loss
.
Br J Haematol
.
2024
;
205
(
1
):
17
-
19
.
29.
Grigg
S
,
Minson
A
,
Prins
E
,
Dickinson
MJ
.
Relapse after glofitamab has a poor prognosis and rates of CD20 loss are high
.
Br J Haematol
.
2024
;
205
(
1
):
122
-
126
.
30.
Schuster
SJ
,
Huw
LY
,
Bolen
CR
, et al
.
Loss of CD20 expression as a mechanism of resistance to mosunetuzumab in relapsed/refractory B-cell lymphomas
.
Blood
.
2024
;
143
(
9
):
822
-
832
.
31.
Sotillo
E
,
Barrett
DM
,
Black
KL
, et al
.
Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy
.
Cancer Discov
.
2015
;
5
(
12
):
1282
-
1295
.
32.
Plaks
V
,
Rossi
JM
,
Chou
J
, et al
.
CD19 target evasion as a mechanism of relapse in large B-cell lymphoma treated with axicabtagene ciloleucel
.
Blood
.
2021
;
138
(
12
):
1081
-
1085
.
33.
Nastoupil
LJ
,
Jain
MD
,
Feng
L
, et al
.
Standard-of-care axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma: results from the US Lymphoma CAR T Consortium
.
J Clin Oncol
.
2020
;
38
(
27
):
3119
-
3128
.
34.
Qualls
DA
,
Lambert
N
,
Caimi
PF
, et al
.
Tafasitamab and lenalidomide in large B-cell lymphoma: real-world outcomes in a multicenter retrospective study
.
Blood
.
2023
;
142
(
26
):
2327
-
2331
.
35.
Di Blasi
R
,
Le Gouill
S
,
Bachy
E
, et al
.
Outcomes of patients with aggressive B-cell lymphoma after failure of anti-CD19 CAR T-cell therapy: a DESCAR-T analysis
.
Blood
.
2022
;
140
(
24
):
2584
-
2593
.
36.
Alarcon Tomas
A
,
Fein
JA
,
Fried
S
, et al
.
Outcomes of first therapy after CD19-CAR-T treatment failure in large B-cell lymphoma
.
Leukemia
.
2023
;
37
(
1
):
154
-
163
.
37.
Birtas Atesoglu
E
,
Gulbas
Z
,
Uzay
A
, et al
.
Glofitamab in relapsed/refractory diffuse large B-cell lymphoma: real-world data
.
Hematol Oncol
.
2023
;
41
(
4
):
663
-
673
.
38.
Shumilov
E
,
Wurm-Kuczera
R
,
Kerkhoff
A
, et al
.
Safety and efficacy of glofitamab for relapsed/refractory large B-cell lymphoma in a multinational real-world study
.
Blood Adv
.
2024
;
9
(
15
):
3865
-
3877
.
39.
Hsu
YT
,
Wu
SJ
,
Kao
HW
, et al
.
Glofitamab as a salvage treatment for B-cell lymphomas in the real world: a multicenter study in Taiwan
.
Cancer
.
2024
;
130
(
11
):
1972
-
1981
.
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