Lisocabtagene maraleucel // Breyanzi
CAR-T ( Chimeric antigen receptor -T cell therapy)
MECHANISM OF ACTION
Mechanism of action: BREYANZI is a CD19-directed genetically modified autologous cell immunotherapy administered as a defined composition to reduce variability in CD8-positive and CD4-positive T cell dose. The CAR is comprised of an FMC63 monoclonal antibody-derived single chain variable fragment (scFv), IgG4 hinge region, CD28 transmembrane domain, 4-1BB (CD137) costimulatory domain, and CD3 zeta activation domain. CD3 zeta signaling is critical for initiating activation and antitumor activity, while 4-1BB (CD137) signaling enhances the expansion and persistence of BREYANZI. CAR binding to CD19 expressed on the cell surface of tumor and normal B cells induces activation and proliferation of CAR T cells, release of pro-inflammatory cytokines, and cytotoxic killing of target cells.
Route of elimination: none known
MECHANISM OF KIDNEY INJURY
74% patients with CRS - AKI (26%) from kidney hypoperfusion vs ATN
CLINICAL KIDNEY SYNDROME
AKI
CARDIOVASCULAR ADVERSE EFFECTS
LYTE ABNORMALITIES
Hyponatremia, Hypomagnesemia, Hypokalemia, Hypophosphatemia
RISK FACTORS
MITIGATION STRATEGIES
n/a
SUGGESTIONS
If CRS - Tocilizumab/steroids
NOTES/COMMENTS
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PHARMACOKINETICS
Molecular Weight
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Volume of Distribution
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Plasma Protein Binding
Metabolism
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Bioavailability
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Half-life elimination
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Time to peak
Maximal expansion in peripheral blood is 12 days after infusion
Excretion
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Dialyzable?
Unknown
REF:
PATHOLOGY SLIDES:
ENTRY UPDATES:
Marco Bonilla
Chicago/USA
Sep 25, 2022