Abstract
The occurrence of a secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) after CAR T-cell infusion is very rare and mostly fatal. Treatment recommendations for such a complication are not yet established. Here, we report the dramatic recovery of HLH/MAS following tisagenlecleucel infusion in a young patient with relapsed acute lymphoblastic leukemia using etoposide phosphate (EP). We propose that monitoring for the occurrence of HLH/MAS should be part of surveillance after CAR T-cell infusion and that EP treatment appears to be useful to control this severe and rare complication.
References
1.
Maude
SL
, Laetsch
TW
, Buechner
J
, Rives
S
, Boyer
M
, Bittencourt
H
, Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia
. N Engl J Med
. 2018 Feb
;378
(5
):439
–48
. .2.
Schuster
SJ
, Svoboda
J
, Chong
EA
, Nasta
SD
, Mato
AR
, Anak
Ö
, Chimeric antigen receptor T cells in refractory B-cell lymphomas
. N Engl J Med
. 2017 Dec
;377
(26
):2545
–54
. .3.
Neelapu
SS
, Locke
FL
, Bartlett
NL
, Lekakis
LJ
, Miklos
DB
, Jacobson
CA
, Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma
. N Engl J Med
. 2017 Dec
;377
(26
):2531
–44
. .4.
Kymriah-epar-product-information
. 2021
. Available from: https://www.ema.europa.eu/documents/product-information/kymriah-epar-product-information_en.pdf (accessed February 12, 2022).5.
Yescarta-epar-product-information
. 2021
. Available from: https://www.ema.europa.eu/en/documents/product-information/yescarta-epar-product-information_en.pdf (accessed February 12, 2022).6.
Neelapu
SS
, Tummala
S
, Kebriaei
P
, Wierda
W
, Gutierrez
C
, Locke
FL
, Chimeric antigen receptor T-cell therapy: assessment and management of toxicities
. Nat Rev Clin Oncol
. 2018 Jan
;15
(1
):47
–62
. .7.
Yáñez
L
, Sánchez-Escamilla
M
, Perales
MA
. CAR T Cell toxicity: current management and future directions
. Hemasphere
. 2019 Mar
;3
(2
):e186
.8.
Penack
O
, Koenecke
C
. Complications after CD19+ CAR T-cell therapy
. Cancers
. 2020 Nov
;12
(11
):3445
. .9.
Sandler
RD
, Tattersall
RS
, Schoemans
H
, Greco
R
, Badoglio
M
, Labopin
M
, Diagnosis and management of secondary HLH/MAS following HSCT and CAR-T cell therapy in adults: a review of the literature and a survey of practice within EBMT Centres on behalf of the autoimmune diseases working party (ADWP) and transplant complications working party (TCWP)
. Front Immunol
. 2020 Mar
;11
:524
. .10.
Lee
DW
, Santomasso
BD
, Locke
FL
, Ghobadi
A
, Turtle
CJ
, Brudno
JN
, ASTCT Consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells
. Biol Blood Marrow Transplant
. 2019 Apr
;25
(4
):625
–38
. .11.
U.S. Department of Health & Human Services
. Common terminology criteria for adverse events (CTCAE)
. 2021
. Available from: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/ (accessed February 12, 2022).12.
Jordan
MB
, Allen
CE
, Weitzman
S
, Filipovich
AH
, McClain
KL
. How I treat hemophagocytic lymphohistiocytosis
. Blood
. 2011 Oct
;118
(15
):4041
–52
. .13.
Schram
AM
, Berliner
N
. How I treat hemophagocytic lymphohistiocytosis in the adult patient
. Blood
. 2015 May
;125
(19
):2908
–14
. .14.
Lee
DW
, Gardner
R
, Porter
DL
, Louis
CU
, Ahmed
N
, Jensen
M
, Current concepts in the diagnosis and management of cytokine release syndrome
. Blood
. 2014 Jul
;124
(2
):188
–95
. .15.
Martín-Rojas
RM
, Gómez-Centurión
I
, Bailén
R
, Bastos
M
, Diaz-Crespo
F
, Carbonell
D
, Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) following treatment with tisagenlecleucel
. Clin Case Rep
. 2022 Jan
;10
(1
):e05209
.16.
Lehmberg
K
, Nichols
KE
, Henter
JI
, Girschikofsky
M
, Greenwood
T
, Jordan
M
, Consensus recommendations for the diagnosis and management of hemophagocytic lymphohistiocytosis associated with malignancies
. Haematologica
. 2015 Aug
;100
(8
):997
–1004
. .17.
Johnson
TS
, Terrell
CE
, Millen
SH
, Katz
JD
, Hildeman
DA
, Jordan
MB
. Etoposide selectively ablates activated T cells to control the immunoregulatory disorder hemophagocytic lymphohistiocytosis
. J Immunol
. 2014 Jan
;192
(1
):84
–91
. .18.
Martín-Rojas
RM
, Gómez-Centurión
I
, Bailén
R
, Bastos
M
, Diaz-Crespo
F
, Carbonell
D
, Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) following treatment with tisagenlecleucel
. Clin Case Rep
. 2022 Jan
;10
(1
):e05209
.19.
Major
A
, Collins
J
, Craney
C
, Heitman
AK
, Bauer
E
, Zerante
E
, Management of hemophagocytic lymphohistiocytosis (HLH) associated with chimeric antigen receptor T-cell (CAR-T) therapy using anti-cytokine therapy: an illustrative case and review of the literature
. Leuk Lymphoma
. 2021 Jul
;62
(7
):1765
–9
. .20.
Shah
NN
, Highfill
SL
, Shalabi
H
, Yates
B
, Jin
J
, Wolters
PL
, CD4/CD8 T-cell selection affects chimeric antigen receptor (CAR) T-cell potency and toxicity: updated results from a phase I anti-CD22 CAR T-cell trial
. J Clin Oncol
. 2020 Jun
;38
(17
):1938
–50
. .21.
Kennedy
VE
, Wong
C
, Huang
CY
, Kambhampati
S
, Wolf
J
, Martin
TG
, Macrophage activation syndrome-like (MAS-L) manifestations following BCMA-directed CAR T cells in multiple myeloma
. Blood Adv
. 2021 Dec
;5
(23
):5344
–8
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