Peringatan Keamanan

Toxicity information regarding brexucabtagene autoleucel is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as severe infections, severe and prolonged cytopenia, hypogammaglobulinemia, cytokine release syndrome, and neurological toxicities.A216188, L15148 Symptomatic and supportive measures are recommended.

Brexucabtagene autoleucel

DB15699

biotech approved

Deskripsi

Mantle cell lymphoma is a heterogeneous sub-category of non-Hodgkin's lymphoma that can be classified as either an aggressive nodal or an indolent leukemic non-nodal variant. Despite the introduction of Bruton's tyrosine kinase (BTK) inhibitors such as ibrutinib and acalabrutinib, the prognosis for MCL patients remains poor and those that relapse following BTK inhibitor therapy have few treatment options.A216153, A216158

More recently, chimeric antigen receptor (CAR) T cell therapies have been developed that modify a patient's own T cells using viral transduction to bind to and destroy cancerous cells. These therapies differ in manufacturing methodology, viral vector, chimeric antigen choice, and the internal co-stimulatory domains of the chimeric antigen.A216188 Similar to axicabtagene ciloleucel, brexucabtagene autoleucel employs a murine anti-CD19 single-chain variable fragment (scFv) linked to internal CD28- and CD3?-derived co-stimulatory domains.A216148, A216163, L15148 However, the preparation of brexucabtagene autoleucel, previously referred to as KTE-X19, uses a method of T cell enrichment that decreases the prevalence of CD19-expressing tumour cells in the CAR T cell preparation.L15148

Brexucabtagene autoleucel was granted accelerated approval for the treatment of relapsed and refractory MCL by the FDA on July 24, 2020, and is currently available through Kite Pharma Inc. under the tradename TECARTUS.L15148

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) -
Volume Distribusi -
Klirens (Clearance) -

Absorpsi

Patients in the ZUMA-2 clinical trial received a target dose of 2 x 106 CAR T cells/kg, which expanded to a variable degree among responders and non-responders; peak levels were reached within the first seven to 15 days following infusion.A216148, L15148 Median peak CAR T cell levels were 102.4 cells/?L (range 0.2 to 2589.5) in responders and 12.0 cells/?L (range 0.2 to 1354.0) in non-responders. The corresponding median AUC0-28 for responders and non-responders was 1487.0 cells/?L\*day (range 3.8 to 2.77E+04) and 169.5 cells/?L\*day (range 1.8 to 1.17E+04), respectively.L15148 These values were also assessed based on the co-administration of immunosuppressive therapy. Patients receiving neither corticosteroids nor tocilizumab had a peak of 24.7 cells/?L with an AUC0-28 of 360.4 cells/?L\*day, patients receiving only corticosteroids had a peak of 24.2 cells/?L and an AUC0-28 of 367.8 cells/?L\*day, and patients receiving only tocilizumab had a peak of 86.5 cells/?L and an AUC0-28 of 1188.9 cells/?L\*day. The highest counts were in patients receiving both corticosteroids and tocilizumab, with a peak of 167.2 cells/?L and an AUC0-28 of 1996.0 cells/?L\*day.L15148 Finally, separating patients into those < 65 years of age of ? 65 years of age, patients in the lower age group had a median peak of 112.5 cells/?L and a median AUC0-28 of 1640.2 cells/?L\*day. Older patients had a median peak count of 74.1 cells/?L and a median AUC0-28 of 876.5 cells/?L\*day.L15148

Metabolisme

Data metabolisme tidak tersedia.

Rute Eliminasi

Data eliminasi belum tersedia.

Interaksi Obat

38 Data
Darbepoetin alfa The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Brexucabtagene autoleucel.
Erythropoietin The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Brexucabtagene autoleucel.
Peginesatide The risk or severity of Thrombosis can be increased when Peginesatide is combined with Brexucabtagene autoleucel.
Methoxy polyethylene glycol-epoetin beta The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Brexucabtagene autoleucel.
Lidocaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Lidocaine.
Ropivacaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Ropivacaine.
Bupivacaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Bupivacaine.
Cinchocaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Cinchocaine.
Dyclonine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Dyclonine.
Procaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Procaine.
Prilocaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Prilocaine.
Proparacaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Proparacaine.
Meloxicam The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Meloxicam.
Oxybuprocaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Oxybuprocaine.
Cocaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Cocaine.
Mepivacaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Mepivacaine.
Levobupivacaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Levobupivacaine.
Diphenhydramine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Diphenhydramine.
Benzocaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Benzocaine.
Chloroprocaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Chloroprocaine.
Phenol The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Phenol.
Tetrodotoxin The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Tetrodotoxin.
Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Benzyl alcohol.
Capsaicin The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Capsaicin.
Etidocaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Etidocaine.
Articaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Articaine.
Tetracaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Tetracaine.
Propoxycaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Propoxycaine.
Pramocaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Pramocaine.
Butamben The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Butamben.
Butacaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Butacaine.
Oxetacaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Oxetacaine.
Ethyl chloride The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Ethyl chloride.
Butanilicaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Butanilicaine.
Metabutethamine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Metabutethamine.
Quinisocaine The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Quinisocaine.
Ambroxol The risk or severity of methemoglobinemia can be increased when Brexucabtagene autoleucel is combined with Ambroxol.
Etrasimod The risk or severity of immunosuppression can be increased when Brexucabtagene autoleucel is combined with Etrasimod.

Target Protein

B-lymphocyte antigen CD19 CD19

Referensi & Sumber

Synthesis reference: Arianne Perez, Stuart A. Sievers, Ruben Alvarez Rodriguez, and Jonathan Belk. "Chimeric antigen receptors and CAR-T cells and methods of use." U.S. Patent US2019065776, issued June 18, 2020.
Artikel (PubMed)
  • PMID: 32242358
    Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT, Timmerman JM, Holmes H, Jaglowski S, Flinn IW, McSweeney PA, Miklos DB, Pagel JM, Kersten MJ, Milpied N, Fung H, Topp MS, Houot R, Beitinjaneh A, Peng W, Zheng L, Rossi JM, Jain RK, Rao AV, Reagan PM: KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma. N Engl J Med. 2020 Apr 2;382(14):1331-1342. doi: 10.1056/NEJMoa1914347.
  • PMID: 30963600
    Jain P, Wang M: Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management. Am J Hematol. 2019 Jun;94(6):710-725. doi: 10.1002/ajh.25487. Epub 2019 Apr 19.
  • PMID: 30154113
    Maddocks K: Update on mantle cell lymphoma. Blood. 2018 Oct 18;132(16):1647-1656. doi: 10.1182/blood-2018-03-791392. Epub 2018 Aug 28.
  • PMID: 29058502
    Roberts ZJ, Better M, Bot A, Roberts MR, Ribas A: Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL. Leuk Lymphoma. 2018 Aug;59(8):1785-1796. doi: 10.1080/10428194.2017.1387905. Epub 2017 Oct 23.
  • PMID: 29910620
    Jain MD, Bachmeier CA, Phuoc VH, Chavez JC: Axicabtagene ciloleucel (KTE-C19), an anti-CD19 CAR T therapy for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin's lymphoma. Ther Clin Risk Manag. 2018 May 31;14:1007-1017. doi: 10.2147/TCRM.S145039. eCollection 2018.
  • PMID: 30528964
    Brudno JN, Kochenderfer JN: Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management. Blood Rev. 2019 Mar;34:45-55. doi: 10.1016/j.blre.2018.11.002. Epub 2018 Nov 14.

Contoh Produk & Brand

Produk: 5 • International brands: 0
Produk
  • Tecartus
    Suspension • 120000000 cells • Intravenous • EU • Approved
  • Tecartus
    Suspension • 200000000 cells / bag • Intravenous • Canada • Approved
  • Tecartus
    Suspension • 100000000 cells / bag • Intravenous • Canada • Approved
  • Tecartus
    Suspension • 1000000 1/68mL • Intravenous • US • Approved
  • Tecartus
    Suspension • 2000000 1/68mL • Intravenous • US • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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