Continuous
blood purification successfully treated a fatal cytokine release
syndrome and immune effector cell-associated neurotoxicity syndrome
after chimeric antigen receptor T cell therapy: case report
Abstract :
Cytokine
release syndrome (CRS) and
Immune
effector Cell-Associated Neurotoxicity Syndrome (ICANS) after
Chimeric
antigen receptor (CAR) T cell treatment are common, and severe CRS
(sCRS) could be life threatening.
IL-6
receptor antibody and steroid are recommended for CRS, but no clear
strategies exist for steroid-resistant sCRS. Thus, this study reported a
case of resistance to tocilizumab and pulse therapy of
methylprednisolone while
suffering
from grade 4 CRS and ICANS. After plasma exchange for two times and
continuous renal replacement treatment combined with ruxolitinib, the
patient survived with only renal injury, and achieved complete remission
with negative minimal residual disease.
Acute lymphoblastic leukemia (ALL) is the most common cancer in
childhood, with B lineage accounting for 75%–85% of all cases(1).
Owing to the development of chemotherapy, B-ALL cure rates exceed 90%
in children, but the cure rate for children with relapsed and/or
refractory (R/R) B-ALL remains low(2, 3). In 2017, the CD19-targeted CAR
T-cell product tisagenlecleucel was approved by the FDA for children and
young adults (aged < 25 years) in R/R B-ALL(4). With the
development of CAR T-cell immunotherapy, the CR rate has reached almost
90% in R/R B-ALL(5, 6).
As a response to CAR T-cell, cytokine release syndrome (CRS) is an
inflammatory syndrome that occurred in 50%–90% of patients after
infusion, with fever, hypoxemia, hypotension requiring multiple
vasopressors, multiple-organ failure (MOF), or even a life-threatening
condition(7). The standardized grading evaluation and first-line
therapies for CRS are well established(7, 8). Immune effector
Cell-Associated Neurotoxicity Syndrome (ICANS) have been described in
30%–64% of patients(9), repetitive seizures or coma have been
described in 10%–20% patients, and 1% of patients died from rapid
cerebral edema(10). For fatal CRS and ICANS, patient transfer to
intensive care unit, mechanical ventilation, multiple vasopressors,
anti-IL-6 therapy, high-dose
methylprednisolone
are recommended(9, 11). However, for patients resistant to
methylprednisolone and tocilizumab, no definite treatment is available
in published guidelines. Herein, a pediatric case of grade 4 CRS and
grade 4 ICANS after CAR T-cell infusion was reported. Through
therapeutic
plasma exchange (TPE) and
continuous
renal replacement therapy (CRRT), CRS was controlled, MOF was improved,
and ultimately, the patient achieved complete remission (CR). To the
authors’ knowledge, this study was the first to report the use of TPE
combined with CRRT for tocilizumab-resistant CRS and ICANS.