DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
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Lisocabtagene maraleucel (liso-cel; JCAR017; Anti-CD19 CAR T-Cells) is an investigational chimeric antigen receptor (CAR) T-cell therapy designed to target CD19, [1][2] which is a surface glycoprotein expressed during normal B-cell development and maintained following malignant transformation of B cells. [3][4][5] Liso-cel CAR T-cells aim to target and CD-19 expressing cells through a CAR construct that includes an anti-CD19 single-chain variable fragment (scFv) targeting domain for antigen specificity, a transmembrane domain, a 4-1BB costimulatory domain hypothesized to increase T-cell proliferation and persistence, and a CD3-zeta T-cell activation domain. [1][2][6][7][8][9] The defined composition of liso-cel may limit product variability; however, the clinical significance of defined composition is unknown. [1][10] Image Courtesy: 2019/2020 Celgene/Juno Therapeutics / Bristol Meyers Squibb.
Lisocabtagene maraleucel
リソカブタゲンマラルユーセル;
JCAR 017
STN# BLA 125714
- Adoptive immunotherapy agent JCAR 017
- Autologous anti-CD19 scFv/4-1BB/CD3ζ/CD28 chimeric antigen receptor-expressing CD4+/CD8+ central memory T cell JCAR 017
- CAR T-cell JCAR 017
FDA 2021, 2021/2/24, BREYANZI
Juno Therapeutics
Antineoplastic, Anti-CD19 CAR-T cell
An immunotherapeutic autologous T cell preparation expressing a chimeric antigen receptor (CAR) specific to the CD19 antigen (Juno Therapeutics, Inc., Seattle, Washington, USA – FDA Clinical Trial Data)
- For the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B.
Lisocabtagene maraleucel, sold under the brand name Breyanzi, is a cell-based gene therapy used to treat large B-cell lymphoma.[1][3]
Side effects of lisocabtagene maraleucel include hypersensitivity reactions, serious infections, low blood cell counts and a weakened immune system.[3]
Lisocabtagene maraleucel, a chimeric antigen receptor (CAR) T cell therapy, is the third gene therapy approved by the U.S. Food and Drug Administration (FDA) for certain types of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL).[3] Lisocabtagene maraleucel was approved for medical use in the United States in February 2021.[1][3]
Medical uses
Lisocabtagene maraleucel is indicated for the treatment of adults with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B.[1][3]
Lisocabtagene maraleucel is not indicated for the treatment of people with primary central nervous system lymphoma.[3]
Adverse effects
The labeling carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T cells, causing high fever and flu-like symptoms and neurologic toxicities.[3]
History
The safety and efficacy of lisocabtagene maraleucel were established in a multicenter clinical trial of more than 250 adults with refractory or relapsed large B-cell lymphoma.[3] The complete remission rate after treatment with lisocabtagene maraleucel was 54%.[3]
The FDA granted lisocabtagene maraleucel orphan drug, regenerative medicine advanced therapy (RMAT) and breakthrough therapy designations.[3] Lisocabtagene maraleucel is the first regenerative medicine therapy with RMAT designation to be licensed by the FDA.[3] The FDA granted approval of Breyanzi to Juno Therapeutics Inc., a Bristol-Myers Squibb Company.[3]
SYN
WO 2018156680
WO 2018183366
Saishin Igaku (2018), 73(11), 1504-1512.
WO 2019148089
WO 2019220369
Leukemia & Lymphoma (2020), 61(11), 2561-2567.
WO 2020097350
WO 2020086943
Journal of Immunotherapy (2020), 43(4), 107-120.
CLIP
On February 5, 2021, the Food and Drug Administration approved lisocabtagene maraleucel (Breyanzi, Juno Therapeutics, Inc.) for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B.
Lisocabtagene maraleucel is a CD19-directed chimeric antigen receptor (CAR) T cell immunotherapy. It consists of autologous T cells that are genetically modified to produce a CAR protein, allowing the T cells to identify and eliminate CD19-expressing normal and malignant cells.
Efficacy was evaluated in TRANSCEND (NCT02631044), a single-arm, open label, multicenter trial that evaluated lisocabtagene maraleucel, preceded by lymphodepleting chemotherapy, in adults with R/R large B-cell lymphoma after at least two lines of therapy.
Of the 192 patients evaluable for response, the overall response rate (ORR) per independent review committee assessment was 73% (95% CI: 67, 80) with a complete response (CR) rate of 54% (95% CI: 47, 61). The median time to first response was one month. Of the 104 patients who achieved CR, 65% had remission lasting at least 6 months and 62% had remission lasting at least 9 months. The estimated median duration of response (DOR) was not reached (95% CI: 16.7 months, NR) in patients who achieved a CR. The estimated median DOR among patients with partial response was 1.4 months (95% CI: 1.1, 2.2).
Cytokine release syndrome (CRS) occurred in 46% of patients (Grade 3 or higher, 4%) and neurologic toxicity occurred in 35% (Grade 3 or higher, 12%). Three patients had fatal neurologic toxicity. Other Grade 3 or higher adverse reactions included infections (19%) and prolonged cytopenias (31%). FDA approved lisocabtagene maraleucel with a Risk Evaluation and Mitigation Strategy because of the risk of fatal or life-threatening CRS and neurologic toxicities.
The recommended regimen is a single dose containing 50 to 110 x 106 CAR-positive viable T cells with a 1:1 ratio of CD4 and CD8 components, administered by IV infusion and preceded by fludarabine and cyclophosphamide for lymphodepletion. Lisocabtagene maraleucel is not indicated for the treatment of patients with primary central nervous system lymphoma.
References
- ^ Jump up to:a b c d “Lisocabtagene maraleucel”. U.S. Food and Drug Administration (FDA). 5 February 2021. Retrieved 5 February 2021.
This article incorporates text from this source, which is in the public domain. - ^ https://www.fda.gov/media/145711/download
- ^ Jump up to:a b c d e f g h i j k l “FDA Approves New Treatment For Adults With Relapsed Or Refractory Large-B-Cell Lymphoma”. U.S. Food and Drug Administration (FDA) (Press release). 5 February 2021. Retrieved 5 February 2021. This article incorporates text from this source, which is in the public domain.
External links
- “Lisocabtagene maraleucel”. NCI Drug Dictionary. National Cancer Institute.
- Clinical trial number NCT02631044 for “Study Evaluating the Safety and Pharmacokinetics of JCAR017 in B-cell Non-Hodgkin Lymphoma (TRANSCEND-NHL-001)” at ClinicalTrials.gov
| Clinical data | |
|---|---|
| Trade names | Breyanzi |
| Other names | JCAR017 |
| License data | US DailyMed: Lisocabtagene_maraleucel |
| Routes of administration | Intravenous |
| ATC code | None |
| Legal status | |
| Legal status | US: ℞-only [1][2] |
| Identifiers | |
| UNII | 7K2YOJ14X0 |
| KEGG | D11990 |
| ChEMBL | ChEMBL4297236 |
///////////Lisocabtagene maraleucel, BREYANZI, FDA 2021, APPROVALS 2021, リソカブタゲンマラルユーセル , Juno Therapeutics, JCAR 017, STN# BLA 125714
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New Drug Approvals 
#Lisocabtagene maraleucel, #BREYANZI, #FDA 2021, #APPROVALS 2021, #リソカブタゲンマラルユーセル , #Juno Therapeutics, #JCAR 017, #STN# BLA 125714