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DCRLIUNGICUAPLDPAETAERSLS
Cytokine Release Syndrome in Patients Receiving Blinatumomab or
Chimeric Antigen Receptor T Cells for Acute Lymphoblastic Leukemia
Craig W. Freyer, PharmD events (AEs) not observed with cytotoxic intensity correlates with disease burden
BCOP chemotherapy. Both blinatumomab and (i.e., marrow blast count); as such, various
Clinical Pharmacy Specialist CAR T cells can cause cytokine release syn- attempts to reduce CRS have emerged
Hematology/Oncology drome (CRS), a potentially life-threatening throughout clinical trial experience with
Hospital of the University inflammatory AE that pharmacists must be blinatumomab, including dexamethasone
of Pennsylvania familiar with to optimize supportive care pretreatment and administration of leuko-
Philadelphia, PA and maximize patient outcomes with these reducing chemotherapy.6,7 The FDA-approved
new immunotherapies. labeling for blinatumomab requires two
Mitchell E. Hughes, PharmD BCPS interventions to reduce CRS: a step-wise
Clinical Pharmacy Specialist CRS following blinatumomab or CAR T dosing approach of 9 mcg/day on days
Hematology/Oncology cells is characterized by symptoms of ex- 1–7 followed by 28 mcg/day on days
Hospital of the University of Pennsylvania cessive inflammation secondary to release 8–28 of cycle 1, as well as dexamethasone
Philadelphia, PA of numerous pro-inflammatory cytokines pretreatment. Dexamethasone 20 mg IV is
following T-cell activation and expansion. administered 1 hour prior to starting the
The U.S. Food and Drug Administration The implicated cytokines include IL-10, cycle 1 day 1 infusion, as well as with the
(FDA) approval of blinatumomab (Blincy- IL-6, IL-2, IFN-γ, and TNF-α, yet the day 8 dose escalation during cycle 1, prior
to®) in December 2014 marked the arrival magnitude of elevation shows significant to day 1 starts for subsequent cycles, and
of immunotherapy for relapsed/refractory interpatient variability.5 Severe febrile anytime the infusion is interrupted for 4
B-cell acute lymphoblastic leukemia (RR episodes (often > 40 °C) are common, hours or more. Pharmacists are instrumen-
B-ALL). Since then, other immunotherapy presenting a challenge to delineate CRS tal in limiting the risk of CRS by ensuring
strategies have emerged, particularly the versus infection. Patients may also experi- appropriate dexamethasone premedication
development of chimeric antigen receptor ence myalgia, headaches, gastrointestinal and providing nursing education to never
(CAR) T-cell clinical trials at some U.S. distress, and fatigue. More severe sequelae flush the line containing blinatumomab,
cancer centers. Blinatumomab is a bispe- include respiratory failure, neurologic tox- as this can increase risk of CRS by giving a
cific T-cell engager antibody fragment that icity (e.g., delirium, tremor, and seizures), sudden bolus of drug to the patient.1
binds CD19 on B cells and CD3 on T cells, cardiovascular compromise, tumor lysis
forming an immunologic synapse resulting syndrome, and disseminated intravascular Treatment of CRS relies on toxicity
in B-cell lysis.1 CAR T cells are virally coagulopathy. Using the FDA-approved grading using the National Cancer
engineered autologous T cells expressing dosing, blinatumomab has a reported CRS Institute Common Terminology Criteria
a CD19 receptor that are capable of in vivo incidence of 11% for all grades and occurs for Adverse Events for CRS. Grade 1 CRS
expansion resulting in T-cell activation and only during the first cycle of treatment consists of symptoms that are not life
tumor lysis.2-4 Both of these CD19 targeted (usually within week 1), with symptoms threatening, such as fever and consti-
immunotherapies display impressive effica- correlating with T-cell expansion. CRS tutional symptoms, which require only
cy in RR B-ALL, yet present new challenges
in supportive care with unique adverse
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