Abstract
Tuberous sclerosis (TS) is a rare autosomal dominant genetic multisystem disease caused by mutations in either the TSC1 or TSC2 gene and results in the growth of non-cancerous masses in several organs. Diffuse large B-cell lymphoma (DLBCL) is the predominant non-Hodgkin lymphoma in adolescents and young adults. Metronomic chemotherapy (mCHEMO) can be defined as the frequent, regular administration of drug doses able to maintain a low, but active, range of concentrations of chemotherapeutic drugs during prolonged periods of time. We present the case of a young woman with severe TS who developed DLBCL. She was treated consecutively with the mCHEMO schedule R-DEVEC (prednisone, vinorelbine, etoposide, cyclophosphamide, plus rituximab) and then ibrutinib, achieving an impressive long-lasting complete remission. In conclusion, alternative treatments could be necessary when comorbidities are present in patients, and mCHEMO can be a potential successful therapeutic approach in frail subjects.
Journal Section:
Anticancer Section / Case Report
References
1.
Osborne
JP
, Fryer
A
, Webb
D
. Epidemiology of tuberous sclerosis
. Ann N Y Acad Sci
. 1991
;615
:125
–7
.2.
Curatolo
P
, Bombardieri
R
, Jozwiak
S
. Tuberous sclerosis
. Lancet
. 2008 Aug
372
9639
657
68
.3.
Hochberg
J
, El-Mallawany
NK
, Abla
O
. Adolescent and young adult non-Hodgkin lymphoma
. Br J Haematol
. 2016 May
173
4
637
50
.4.
Kahn
JM
, Ozuah
NW
, Dunleavy
K
, Henderson
TO
, Kelly
K
, LaCasce
A
. Adolescent and young adult lymphoma: collaborative efforts toward optimizing care and improving outcomes
. Blood Adv
. 2017 Oct
1
22
1945
58
.5.
de Groen
RAL
, Schrader
AMR
, Kersten
MJ
, Pals
ST
, Vermaat
JSP
. MYD88 in the driver’s seat of B-cell lymphomagenesis: from molecular mechanisms to clinical implications
. Haematologica
. 2019 Dec
104
12
2337
48
.6.
Hartleben
G
, Müller
C
, Krämer
A
, Schimmel
H
, Zidek
LM
, Dornblut
C
et al. Tuberous sclerosis complex is required for tumor maintenance in MYC-driven Burkitt’s lymphoma
. EMBO J
. 2018 Nov
37
21
e98589
.7.
Campo
E
. MYC in DLBCL: partners matter
. Blood
. 2015 Nov
126
22
2439
40
.8.
Perini
GF
, Campregher
PV
, Ross
JS
, Ali
S
, Hamerschlak
N
, Santos
FPS
. Clinical response to everolimus in a patient with Hodgkin’s lymphoma harboring a TSC2 mutation
. Blood Cancer J
. 2016 May
6
5
e420
.9.
Bocci
G
, Kerbel
RS
. Pharmacokinetics of metronomic chemotherapy: a neglected but crucial aspect
. Nat Rev Clin Oncol
. 2016 Nov
13
11
659
73
.10.
Natale
G
, Bocci
G
. Does metronomic chemotherapy induce tumor angiogenic dormancy? A review of available preclinical and clinical data
. Cancer Lett
. 2018 Sep
432
28
37
.11.
Cox
MC
, Bocci
G
. Metronomic chemotherapy regimens and targeted therapies in non-Hodgkin lymphoma: the best of two worlds
. Cancer Lett
. 2022 Jan
524
144
50
.12.
Banchi
M
, Fini
E
, Crucitta
S
, Bocci
G
. Metronomic chemotherapy in pediatric oncology: from preclinical evidence to clinical studies
. J Clin Med
. 2022 Oct
11
21
6254
.13.
Cox
MC
, Musuraca
G
, Battistini
R
, Casaroli
I
, Zoli
V
, Anticoli-Borza
P
et al. Aggressive lymphomas of the elderly: the DEVEC metronomic chemotherapy schedule fits the unfit
. Br J Haematol
. 2018
;183
(5
):819
–22
.14.
Cox
MC
, Pelliccia
S
, Marcheselli
L
, Battistini
R
, Arcari
A
, Borza
PA
et al. The metronomic all-oral DEVEC is an effective schedule in elderly patients with diffuse large b-cell lymphoma
. Invest New Drugs
. 2019 Jun
37
3
548
58
.15.
Cox
MC
, Banchi
M
, Pelliccia
S
, Di Napoli
A
, Marcheselli
L
, Patti
C
et al. All-oral metronomic DEVEC schedule in elderly patients with peripheral T cell lymphoma
. Cancer Chemother Pharmacol
. 2020
;86
(6
):841
–6
.16.
Bocci
G
, Pelliccia
S
, Orlandi
P
, Caridi
M
, Banchi
M
, Musuraca
G
et al. Remarkable remission rate and long-term efficacy of upfront metronomic chemotherapy in elderly and frail patients, with diffuse large B-cell lymphoma
. J Clin Med
. 2022 Dec
11
23
7162
.17.
Vermaat
JS
, Somers
SF
, de Wreede
LC
, Kraan
W
, de Groen
RAL
, Schrader
AMR
et al. MYD88 mutations identify a molecular subgroup of diffuse large B-cell lymphoma with an unfavorable prognosis
. Haematologica
. 2020
;105
(2
):424
–34
.18.
Wilson
WH
, Young
RM
, Schmitz
R
, Yang
Y
, Pittaluga
S
, Wright
G
et al. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma
. Nat Med
. 2015 Aug
21
8
922
6
.19.
Hohloch
K
, Zeynalova
S
, Held
G
, Ziepert
M
, Loeffler
M
, Wulf
G
et al. Excellent outcome of young adults with aggressive non-Hodgkin lymphomas treated with CHOP-like regimens
. Leukemia
. 2014 Nov
28
11
2260
3
.20.
Younes
A
, Sehn
LH
, Johnson
P
, Zinzani
PL
, Hong
X
, Zhu
J
et al. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non–germinal center B-cell diffuse large B-cell lymphoma
. J Clin Oncol
. 2019
;37
(15
):1285
–95
.21.
Inoki
K
, Li
Y
, Zhu
T
, Wu
J
, Guan
K-L
. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
. Nat Cell Biol
. 2002 Sep
4
9
648
57
.22.
Kim
E
, Hurtz
C
, Koehrer
S
, Wang
Z
, Balasubramanian
S
, Chang
BY
et al. Ibrutinib inhibits pre-BCR(+) B-cell acute lymphoblastic leukemia progression by targeting BTK and BLK
. Blood
. 2017 Mar
129
9
1155
65
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