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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

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