Background: The treatment of relapsed/refractory (R/R) peripheral T cell lymphoma (PTCL) is limited to a few agents. Romidepsin, a histone deacetylase inhibitor, was approved for PTCL treatment as a single agent in the R/R setting, yet with partial efficacy. Several attempts to combine romidepsin with other chemotherapy regimens have been reported, however, with significant toxicity. Objectives: To study the romidepsin-bendamustine combination in PTCL in an attempt to maximize efficacy while minimizing toxicity. Methods: We report on a series of 7 heavily pretreated PTCL patients (2–5 previous lines of therapy) treated with a romidepsin-bendamustine combination. Results: Four patients were not previously exposed to either drug. Of these, 2 achieved complete remission. Interestingly, 1 patient continued treatment with a prolonged progression-free survival of more than 4 years. Toxicity was minimal and no treatment-related deaths or discontinuation were noted. Significant nausea and vomiting were reported in over 50% of patients. Hematological toxicity was mild and lower than that reported for other romidepsin-chemotherapy combinations and was correlated with bone marrow involvement by lymphoma. Conclusions: Although reporting a small number of patients, our data suggest that the combination of romidepsin and bendamustine may be a feasible therapeutic option in R/R PTCL patients and merits further study.

1.
Swerdlow
SH
,
Campo
E
,
Pileri
SA
,
Harris
NL
,
Stein
H
,
Siebert
R
, et al.
The 2016 revision of the World Health Organization classification of lymphoid neoplasms
.
Blood
.
2016
May
;
127
(
20
):
2375
90
.
[PubMed]
0006-4971
2.
Broccoli
A
,
Zinzani
PL
.
Peripheral T-cell lymphoma, not otherwise specified
.
Blood
.
2017
Mar
;
129
(
9
):
1103
12
.
[PubMed]
0006-4971
3.
Piekarz
RL
,
Frye
R
,
Prince
HM
,
Kirschbaum
MH
,
Zain
J
,
Allen
SL
, et al.
Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma
.
Blood
.
2011
Jun
;
117
(
22
):
5827
34
.
[PubMed]
0006-4971
4.
Santini
V
,
Gozzini
A
,
Ferrari
G
.
Histone deacetylase inhibitors: molecular and biological activity as a premise to clinical application
.
Curr Drug Metab
.
2007
May
;
8
(
4
):
383
93
.
[PubMed]
1389-2002
5.
Imai
Y
,
Maru
Y
,
Tanaka
J
.
Action mechanisms of histone deacetylase inhibitors in the treatment of hematological malignancies
.
Cancer Sci
.
2016
Nov
;
107
(
11
):
1543
9
.
[PubMed]
1347-9032
6.
Coiffier
B
,
Pro
B
,
Prince
HM
,
Foss
F
,
Sokol
L
,
Greenwood
M
, et al.
Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy
.
J Clin Oncol
.
2012
Feb
;
30
(
6
):
631
6
.
[PubMed]
0732-183X
7.
Pro
B
,
Horwitz
SM
,
Prince
HM
,
Foss
FM
,
Sokol
L
,
Greenwood
M
, et al.
Romidepsin induces durable responses in patients with relapsed or refractory angioimmunoblastic T-cell lymphoma
.
Hematol Oncol
.
2017
Dec
;
35
(
4
):
914
7
.
[PubMed]
0278-0232
8.
Valdez
BC
,
Brammer
JE
,
Li
Y
,
Murray
D
,
Liu
Y
,
Hosing
C
, et al.
Romidepsin targets multiple survival signaling pathways in malignant T cells
.
Blood Cancer J
.
2015
Oct
;
5
(
10
):
e357
.
[PubMed]
2044-5385
9.
Conti
C
,
Leo
E
,
Eichler
GS
,
Sordet
O
,
Martin
MM
,
Fan
A
, et al.
Inhibition of histone deacetylase in cancer cells slows down replication forks, activates dormant origins, and induces DNA damage
.
Cancer Res
.
2010
Jun
;
70
(
11
):
4470
80
.
[PubMed]
0008-5472
10.
Strati
P
,
Chihara
D
,
Oki
Y
,
Fayad
LE
,
Fowler
N
,
Nastoupil
L
, et al.
: A phase I study of romidepsin and ifosfamide, carboplatin, etoposide for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma. Haematologica 2018;haematol.
2018
.187617.
11.
Dupuis
J
,
Morschhauser
F
,
Ghesquières
H
,
Tilly
H
,
Casasnovas
O
,
Thieblemont
C
, et al.
Combination of romidepsin with cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated patients with peripheral T-cell lymphoma: a non-randomised, phase 1b/2 study
.
Lancet Haematol
.
2015
Apr
;
2
(
4
):
e160
5
.
[PubMed]
2352-3026
12.
Reboursiere
E
,
Le Bras
F
,
Herbaux
C
,
Gyan
E
,
Clavert
A
,
Morschhauser
F
, et al.;
From the Lymphoma Study Association (LYSA) centers
.
Bendamustine for the treatment of relapsed or refractory peripheral T cell lymphomas: A French retrospective multicenter study
.
Oncotarget
.
2016
Dec
;
7
(
51
):
85573
83
.
[PubMed]
1949-2553
13.
Damaj
G
,
Gressin
R
,
Bouabdallah
K
,
Cartron
G
,
Choufi
B
,
Gyan
E
, et al.
Results from a prospective, open-label, phase II trial of bendamustine in refractory or relapsed T-cell lymphomas: the BENTLY trial
.
J Clin Oncol
.
2013
Jan
;
31
(
1
):
104
10
.
[PubMed]
0732-183X
14.
Leoni
LM
,
Hartley
JA
.
Mechanism of action: the unique pattern of bendamustine-induced cytotoxicity
.
Semin Hematol
.
2011
Apr
;
48
Suppl 1
:
S12
23
.
[PubMed]
0037-1963
15.
Fernández-Rodríguez
C
,
Salar
A
,
Navarro
A
,
Gimeno
E
,
Pairet
S
,
Camacho
L
, et al.
Anti-tumor activity of the combination of bendamustine with vorinostat in diffuse large B-cell lymphoma cells
.
Leuk Lymphoma
.
2016
;
57
(
3
):
692
9
.
[PubMed]
1042-8194
16.
Cheson
BD
,
Fisher
RI
,
Barrington
SF
,
Cavalli
F
,
Schwartz
LH
,
Zucca
E
, et al.;
Alliance, Australasian Leukaemia and Lymphoma Group
;
Eastern Cooperative Oncology Group
;
European Mantle Cell Lymphoma Consortium
;
Italian Lymphoma Foundation
;
European Organisation for Research
;
Treatment of Cancer/Dutch Hemato-Oncology Group
;
Grupo Español de Médula Ósea
;
German High-Grade Lymphoma Study Group
;
German Hodgkin’s Study Group
;
Japanese Lymphorra Study Group
;
Lymphoma Study Association
;
NCIC Clinical Trials Group
;
Nordic Lymphoma Study Group
;
Southwest Oncology Group
;
United Kingdom National Cancer Research Institute
.
Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification
.
J Clin Oncol
.
2014
Sep
;
32
(
27
):
3059
68
.
[PubMed]
0732-183X
17.
Amengual
JE
,
Lichtenstein
R
,
Lue
J
,
Sawas
A
,
Deng
C
,
Lichtenstein
E
, et al.
A phase 1 study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma
.
Blood
.
2018
Jan
;
131
(
4
):
397
407
.
[PubMed]
0006-4971
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