Serious side effects occur in most patients.[6] The most common serious side effects are cytokine release syndrome (a potentially life-threatening condition that can cause fever, vomiting, shortness of breath, pain and low blood pressure) and decreases in platelets (components that help the blood to clot), hemoglobin (the protein found in red blood cells that carries oxygen around the body) or white blood cells including neutrophils and lymphocytes.[6] Serious infections occur in around three in ten diffuse large B-cell lymphoma (DLBCL) patients.[6]
T cells from a person with cancer are removed, genetically engineered to make a specific chimeric cell surface receptor with components from both a T-cell receptor and an antibody specific to a protein on the cancer cell, and transferred back to the person. The T cells are engineered to target a protein called CD19 that is common on B cells. A chimeric T cell receptor ("CAR-T") is expressed on the surface of the T cell.[medical citation needed]
It was invented and initially developed at the University of Pennsylvania; Novartis completed development, obtained FDA approval, and markets the treatment.[7] In August 2017, it became the first FDA-approved treatment that included a gene therapy step in the United States.[5]
Tisagenlecleucel is indicated for the treatment of those under 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse; or adults 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, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma.[3][6]
In May 2022, the indication in the US was updated to include the treatment of adults with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.[8]
Serious side effects occur in most patients.[6] The most common serious side effects are cytokine release syndrome (a potentially life-threatening condition that can cause fever, vomiting, shortness of breath, pain and low blood pressure) and decreases in platelets (components that help the blood to clot), hemoglobin (the protein found in red blood cells that carries oxygen around the body) or white blood cells including neutrophils and lymphocytes.[6] Serious infections occur in around three in ten diffuse large B-cell lymphoma (DLBCL) patients.[6]
History
The treatment was developed by a group headed by Carl H. June at the University of Pennsylvania, and is licensed to Novartis.[10]
In July 2017, an FDA advisory committee unanimously recommended that the agency approve it to treat B cell acute lymphoblastic leukemia that did not respond adequately to other treatments or have relapsed.[9][12][13]
In August 2017, the FDA granted approval for the use of tisagenlecleucel in people with acute lymphoblastic leukemia.[14][15][16] According to Novartis, the treatment will be administered at specific medical centers where staff have been trained to manage possible reactions to this new type of treatment.[17]
In May 2018, the FDA further approved tisagenlecleucel to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), based on results from the JULIET phase II trial.[14][18]
In England, the NHS will use the procedure to treat children with acute lymphoblastic leukemia (ALL) if earlier treatments including stem cell transplants have failed; it is expected to apply to between 15 and 20 children.[19] In March 2019, NICE issued guidance approving Kymriah for treatment of relapsed or refractory diffuse large B-cell lymphoma in adults after 2 or more systemic therapies.[20]
Manufacture
In a 22-day process, the treatment is customized for each person. T cells are purified from blood drawn from the person, and those cells are then modified by a virus that inserts a gene into the cells' genome. The gene encodes a chimaeric antigen receptor (CAR) that targets leukaemia cells.[12] It uses the 4-1BB co-stimulatory domain in its CAR to improve response.[21]
Modification of the cells to create the customized therapeutic has been a major bottleneck in expanding availability of the treatment, requiring T cells extracted in Europe to be transported to the United States where they are modified, then back to Europe.[22] Novartis has been expanding a facility in France, and constructed a new facility in Stein, Switzerland, to relieve this bottleneck beginning in 2020.[22] Novartis uses the company Cryoport Inc. for temperature-controlled transportation required for the manufacture and distribution of Kymriah.[23][24]
References
^"Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 12 May 2022. Retrieved 13 May 2022.
^"Summary Basis of Decision (SBD) for Kymriah". Health Canada. 23 October 2014. Retrieved 29 May 2022.
^ abc"Kymriah- tisagenlecleucel injection, suspension". DailyMed. 14 June 2019. Retrieved 1 April 2020.
^"Kymriah (tisagenlecleucel)". U.S. Food and Drug Administration. 7 July 2022. Retrieved 19 November 2022.
^ ab"FDA approval brings first gene therapy to the United States". U.S. Food & Drug Administration (FDA) (Press release). Retrieved 31 August 2017.
^"FDA approves tisagenlecleucel". U.S. Food and Drug Administration. 31 May 2022. Retrieved 1 June 2022. This article incorporates text from this source, which is in the public domain.
^ ab. The New York Times. Reuters. 12 July 2017. Archived from the original on 14 July 2017.
^Grady D (12 July 2017). "F.D.A. Panel Recommends Approval for Gene-Altering Leukemia Treatment". The New York Times. Retrieved 1 April 2020.
^"Novartis gets second CAR-T candidate FDA 'breakthrough' tag". www.fiercebiotech.com. Fierce Biotech. 18 April 2017.
^ abLedford H (July 2017). "Engineered cell therapy for cancer gets thumbs up from FDA advisers". Nature. 547 (7663): 270. Bibcode:2017Natur.547..270L. doi:10.1038/nature.2017.22304. PMID 28726836.
^Stein R (12 July 2017). "'Living Drug' That Fights Cancer By Harnessing The Immune System Clears Key Hurdle". NPR. Retrieved 13 July 2017.
^"FDA approval brings first gene therapy to the United States". U.S. Food and Drug Administration (FDA) (Press release). Retrieved 6 September 2017.
^Harris E (27 November 2019). "Challenges Facing The Cell And Gene Sector's Regulation Landscape". Life Science Leader. Pennsylvania, United States: VertMarkets. Retrieved 13 December 2019. After Kymriah (Novartis), Yescarta (Gilead), and Luxturna (Spark) were approved in the U.S. in 2017, they were subsequently approved in 2018 in the EU. Kymriah also has received approval in Australia and an additional indication in the U.S.
^Grady D (30 August 2017). "F.D.A. Approves First Gene-Altering Leukemia Treatment, Costing $475,000". The New York Times. Retrieved 6 September 2017.
^"FDA Expands Tisagenlecleucel Approval - The ASCO Post". www.ascopost.com.
^Sarah Boseley (5 September 2018). "NHS to treat young cancer patients with expensive 'game changer' drug". The Guardian. Retrieved 5 September 2018.
^"Overview | Tisagenlecleucel for treating relapsed or refractory diffuse large B-cell lymphoma after 2 or more systemic therapies | Guidance | NICE". www.nice.org.uk. Retrieved 3 August 2021.
^"FDA Panel Unanimously Recommends Approval for Novartis' CAR T-Cell Therapy CTL019". GEN. GEN Genetic Engineering & Biotechnology News. 13 July 2017.
^ abMiller J (28 November 2019). "Novartis's $90 million Swiss factory to help solve cell therapy bottleneck". Reuters. Retrieved 1 December 2019.
^"Cryoport's CEO on cell therapies' market 'robust demand'". biopharma-reporter.com. Retrieved 18 October 2019.
^"Cryoport talks compliance, biopharma expansion, and Brexit". outsourcing-pharma.com. Retrieved 18 October 2019.
Further reading
BLA 125646 Tisagenlecleucel - Novartis Briefing document to FDA ODAC
External links
"Tisagenlecleucel-T". Drug Information Portal. U.S. National Library of Medicine.
tisagenlecleucel, sold, under, brand, name, kymriah, cells, medication, treatment, cell, acute, lymphoblastic, leukemia, which, uses, body, cells, fight, cancer, adoptive, cell, transfer, clinical, datapronunciationtis, ˌtɪsədʒen, leklusel, trade, nameskymriah. Tisagenlecleucel sold under the brand name Kymriah is a CAR T cells medication for the treatment of B cell acute lymphoblastic leukemia ALL which uses the body s own T cells to fight cancer adoptive cell transfer 5 3 TisagenlecleucelClinical dataPronunciationtis a jen lek loo se ˌtɪsedʒen leklusel Trade namesKymriahOther namesCTL019 CART 19AHFS Drugs comProfessional Drug FactsMedlinePlusa617053License dataEU EMA by INN US DailyMed TisagenlecleucelPregnancycategoryAU C 1 Routes ofadministrationIntravenousATC codeL01XL04 WHO Legal statusLegal statusAU S4 Prescription only CA only 2 US only 3 4 EU Rx onlyPharmacokinetic dataElimination half life16 8 daysIdentifiersCAS Number1823078 37 0DrugBankDB13881UNIIQ6C9WHR03OKEGGD11386Serious side effects occur in most patients 6 The most common serious side effects are cytokine release syndrome a potentially life threatening condition that can cause fever vomiting shortness of breath pain and low blood pressure and decreases in platelets components that help the blood to clot hemoglobin the protein found in red blood cells that carries oxygen around the body or white blood cells including neutrophils and lymphocytes 6 Serious infections occur in around three in ten diffuse large B cell lymphoma DLBCL patients 6 T cells from a person with cancer are removed genetically engineered to make a specific chimeric cell surface receptor with components from both a T cell receptor and an antibody specific to a protein on the cancer cell and transferred back to the person The T cells are engineered to target a protein called CD19 that is common on B cells A chimeric T cell receptor CAR T is expressed on the surface of the T cell medical citation needed It was invented and initially developed at the University of Pennsylvania Novartis completed development obtained FDA approval and markets the treatment 7 In August 2017 it became the first FDA approved treatment that included a gene therapy step in the United States 5 Contents 1 Medical uses 2 Adverse effects 3 History 4 Manufacture 5 References 6 Further reading 7 External linksMedical uses EditTisagenlecleucel is indicated for the treatment of those under 25 years of age with B cell precursor acute lymphoblastic leukemia ALL that is refractory or in second or later relapse or adults 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 high grade B cell lymphoma and DLBCL arising from follicular lymphoma 3 6 In May 2022 the indication in the US was updated to include the treatment of adults with relapsed or refractory follicular lymphoma FL after two or more lines of systemic therapy 8 Adverse effects EditA frequent side effect seen is cytokine release syndrome CRS 7 9 Serious side effects occur in most patients 6 The most common serious side effects are cytokine release syndrome a potentially life threatening condition that can cause fever vomiting shortness of breath pain and low blood pressure and decreases in platelets components that help the blood to clot hemoglobin the protein found in red blood cells that carries oxygen around the body or white blood cells including neutrophils and lymphocytes 6 Serious infections occur in around three in ten diffuse large B cell lymphoma DLBCL patients 6 History EditThe treatment was developed by a group headed by Carl H June at the University of Pennsylvania and is licensed to Novartis 10 In April 2017 tisagenlecleucel received breakthrough therapy designation by the U S Food and Drug Administration FDA for the treatment of relapsed or refractory diffuse large B cell lymphoma 11 In July 2017 an FDA advisory committee unanimously recommended that the agency approve it to treat B cell acute lymphoblastic leukemia that did not respond adequately to other treatments or have relapsed 9 12 13 In August 2017 the FDA granted approval for the use of tisagenlecleucel in people with acute lymphoblastic leukemia 14 15 16 According to Novartis the treatment will be administered at specific medical centers where staff have been trained to manage possible reactions to this new type of treatment 17 In May 2018 the FDA further approved tisagenlecleucel to treat adults with relapsed or refractory diffuse large B cell lymphoma DLBCL based on results from the JULIET phase II trial 14 18 In England the NHS will use the procedure to treat children with acute lymphoblastic leukemia ALL if earlier treatments including stem cell transplants have failed it is expected to apply to between 15 and 20 children 19 In March 2019 NICE issued guidance approving Kymriah for treatment of relapsed or refractory diffuse large B cell lymphoma in adults after 2 or more systemic therapies 20 Manufacture EditIn a 22 day process the treatment is customized for each person T cells are purified from blood drawn from the person and those cells are then modified by a virus that inserts a gene into the cells genome The gene encodes a chimaeric antigen receptor CAR that targets leukaemia cells 12 It uses the 4 1BB co stimulatory domain in its CAR to improve response 21 Modification of the cells to create the customized therapeutic has been a major bottleneck in expanding availability of the treatment requiring T cells extracted in Europe to be transported to the United States where they are modified then back to Europe 22 Novartis has been expanding a facility in France and constructed a new facility in Stein Switzerland to relieve this bottleneck beginning in 2020 22 Novartis uses the company Cryoport Inc for temperature controlled transportation required for the manufacture and distribution of Kymriah 23 24 References Edit Updates to the Prescribing Medicines in Pregnancy database Therapeutic Goods Administration TGA 12 May 2022 Retrieved 13 May 2022 Summary Basis of Decision SBD for Kymriah Health Canada 23 October 2014 Retrieved 29 May 2022 a b c Kymriah tisagenlecleucel injection suspension DailyMed 14 June 2019 Retrieved 1 April 2020 Kymriah tisagenlecleucel U S Food and Drug Administration 7 July 2022 Retrieved 19 November 2022 a b FDA approval brings first gene therapy to the United States U S Food amp Drug Administration FDA Press release Retrieved 31 August 2017 a b c d e f g Kymriah EPAR European Medicines Agency EMA Retrieved 15 August 2020 Text was copied from this source which is c European Medicines Agency Reproduction is authorized provided the source is acknowledged a b BLA 125646 Tisagenlecleucel Novartis Briefing document to FDA ODAC PDF Food and Drug Administration FDA approves tisagenlecleucel U S Food and Drug Administration 31 May 2022 Retrieved 1 June 2022 This article incorporates text from this source which is in the public domain a b FDA Panel Backs Novartis Pioneering New Cancer Gene Therapy The New York Times Reuters 12 July 2017 Archived from the original on 14 July 2017 Grady D 12 July 2017 F D A Panel Recommends Approval for Gene Altering Leukemia Treatment The New York Times Retrieved 1 April 2020 Novartis gets second CAR T candidate FDA breakthrough tag www fiercebiotech com Fierce Biotech 18 April 2017 a b Ledford H July 2017 Engineered cell therapy for cancer gets thumbs up from FDA advisers Nature 547 7663 270 Bibcode 2017Natur 547 270L doi 10 1038 nature 2017 22304 PMID 28726836 Stein R 12 July 2017 Living Drug That Fights Cancer By Harnessing The Immune System Clears Key Hurdle NPR Retrieved 13 July 2017 a b Kymriah tisagenlecleucel U S Food and Drug Administration FDA 1 April 2018 Retrieved 1 April 2020 FDA approval brings first gene therapy to the United States U S Food and Drug Administration FDA Press release Retrieved 6 September 2017 Harris E 27 November 2019 Challenges Facing The Cell And Gene Sector s Regulation Landscape Life Science Leader Pennsylvania United States VertMarkets Retrieved 13 December 2019 After Kymriah Novartis Yescarta Gilead and Luxturna Spark were approved in the U S in 2017 they were subsequently approved in 2018 in the EU Kymriah also has received approval in Australia and an additional indication in the U S Grady D 30 August 2017 F D A Approves First Gene Altering Leukemia Treatment Costing 475 000 The New York Times Retrieved 6 September 2017 FDA Expands Tisagenlecleucel Approval The ASCO Post www ascopost com Sarah Boseley 5 September 2018 NHS to treat young cancer patients with expensive game changer drug The Guardian Retrieved 5 September 2018 Overview Tisagenlecleucel for treating relapsed or refractory diffuse large B cell lymphoma after 2 or more systemic therapies Guidance NICE www nice org uk Retrieved 3 August 2021 FDA Panel Unanimously Recommends Approval for Novartis CAR T Cell Therapy CTL019 GEN GEN Genetic Engineering amp Biotechnology News 13 July 2017 a b Miller J 28 November 2019 Novartis s 90 million Swiss factory to help solve cell therapy bottleneck Reuters Retrieved 1 December 2019 Cryoport s CEO on cell therapies market robust demand biopharma reporter com Retrieved 18 October 2019 Cryoport talks compliance biopharma expansion and Brexit outsourcing pharma com Retrieved 18 October 2019 Further reading EditBLA 125646 Tisagenlecleucel Novartis Briefing document to FDA ODACExternal links Edit Tisagenlecleucel T Drug Information Portal U S National Library of Medicine Portal Medicine Retrieved from https en wikipedia org w index php title Tisagenlecleucel amp oldid 1130661123, wikipedia, wiki, book, books, library,
