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DRUG:

Kymriah (tisagenlecleucel-T)

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Other names: CART 19, CTL019, CTL-019, anti-CD19-CAR retroviral vector-transduced autologous T cells, autologous T cells loaded with a lentiviral vector expressing CART-19, autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR Zeta and 4-1 BB co-stimulatory domains, LG-740, CART 019, anti-CD19-CAR retroviral vector-transduced autologous T cells, Tisa-cel, CART-19, CTL 019, LG 740, LG740
Company:
Novartis, University of Pennsylvania
Drug class:
CD19-targeted CAR-T immunotherapy
Related drugs:
5d
Ph I/II Study of E7777 Prior to CAR-T for R/R LBCL (clinicaltrials.gov)
P1/2, N=30, Suspended, Masonic Cancer Center, University of Minnesota | Trial completion date: Dec 2025 --> Dec 2026 | Recruiting --> Suspended | Trial primary completion date: Dec 2025 --> Sep 2026
Trial completion date • Trial suspension • Trial primary completion date
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
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LDH elevation
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cyclophosphamide • Yescarta (axicabtagene ciloleucel) • Breyanzi (lisocabtagene maraleucel) • Kymriah (tisagenlecleucel-T) • fludarabine IV • Lymphir (denileukin diftitox-cxdl)
5d
Tisagenlecleucel in combination with ibrutinib in adults with relapsed and/or refractory large B-cell lymphomas. (PubMed, Blood Neoplasia)
Altogether, these findings suggest administering ibrutinib before leukapheresis may modify T-cell characteristics in the collected material, thereby improving final CAR T-cell product quality and clinical outcomes for patients with R/R LBLC treated with tisagenlecleucel. This trial was registered at www.clinicaltrials.gov as #NCT03876028.
Clinical • Journal
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IFNG (Interferon, gamma) • IL2 (Interleukin 2)
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Imbruvica (ibrutinib) • Kymriah (tisagenlecleucel-T)
7d
Impact of CD5 expression on outcomes for chimeric antigen receptor-T cell therapy in relapsed and refractory diffuse large B-cell lymphoma. (PubMed, Cytotherapy)
To investigate this clinical issue, 106 patients treated with CAR-T cell therapy using either tisagenlecleucel, lisocabtagene maraleucel or axicabtagene ciloleucel for r/r DLBCL at our institution were retrospectively analyzed. Multivariate analysis revealed that CD5 expression was unfavorably associated with PFS and OS. Together, these data suggest that CD5 expression has a negative impact on outcomes after CAR-T cell therapy.
Journal • IO biomarker
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CD5 (CD5 Molecule)
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Yescarta (axicabtagene ciloleucel) • Breyanzi (lisocabtagene maraleucel) • Kymriah (tisagenlecleucel-T)
15d
Impact of inotuzumab ozogamicin as bridging therapy and tumor burden in CAR-T therapy for B-acute lymphoblastic leukemia. (PubMed, Front Immunol)
This study analyzed 24 R/R ALL patients receiving tisagenlecleucel after BT (Inotuzumab [n=10] vs. chemotherapy/steroids [n=14]). Overall, inotuzumab as BT effectively reduces tumor burden but attenuates CAR-T expansion without compromising survival outcomes. As high tumor burden is a dominant driver of relapse and toxicity, the net effect of inotuzumab may be favorable in selected patients.
Journal
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CD8 (cluster of differentiation 8)
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Besponsa (inotuzumab ozogamicin) • Kymriah (tisagenlecleucel-T)
1m
A Tetrameric Biotin-Avidin Scaffold Using Anti-CD19 (FMC63) Traptavidin Fusion Enables High-Avidity CAR-T Cells for Leukemia Therapy. (PubMed, Bioconjug Chem)
Notably, tCAR-T exhibited superior antitumor activity compared to Kymriah, with enhanced cytokine release and improved target cell elimination. This innovative approach improves cancer treatment efficacy through enhanced binding avidity and modular targeting flexibility, demonstrating that tCAR-T can overcome limitations of conventional CAR-T therapy and highlighting its potential to improve therapeutic outcomes for cancer patients.
Journal
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CD8 (cluster of differentiation 8)
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Kymriah (tisagenlecleucel-T)
1m
Immune Effector Cell-Associated HLH-Like Syndrome (IEC-HS) in CAR-T and TCE-Treated Myeloma and B-Cell Malignancies: Insights from a Pharmacovigilance Study. (PubMed, Transplant Cell Ther)
IEC-HS is a rare but potentially fatal complication. Our disproportionality analysis identifies significant reporting signals for tisa-cel and cilta-cel. The high absolute number of cases observed for products like axi-cel appears to reflect high utilization rather than a disproportionate risk, underscoring the necessity of using statistical signal detection methods when interpreting spontaneous reports.
Journal • Adverse events
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ROR1 (Receptor Tyrosine Kinase Like Orphan Receptor 1)
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Yescarta (axicabtagene ciloleucel) • Breyanzi (lisocabtagene maraleucel) • Kymriah (tisagenlecleucel-T) • Epkinly (epcoritamab-bysp) • Elrexfio (elranatamab-bcmm) • Tecartus (brexucabtagene autoleucel) • Abecma (idecabtagene vicleucel) • Carvykti (ciltacabtagene autoleucel) • Lunsumio (mosunetuzumab-axgb) • Talvey (talquetamab-tgvs) • Tecvayli (teclistamab-cqyv) • Columvi (glofitamab-gxbm)
1m
Emerging role of lisocabtagene maraleucel chimeric antigen receptor-T cell in nodal and gastrointestinal follicular lymphoma. (PubMed, World J Gastroenterol)
Comparative insights highlight the advantages of liso-cel over other CAR-T cell products, such as axicabtagene ciloleucel and tisagenlecleucel in terms of toxicity, logistics, and outpatient feasibility. With ongoing improvements in manufacturing, accessibility, and biomarker development, liso-cel is well-positioned to become a central component in the evolving treatment paradigm for FL. However, challenges remain regarding durability of response, cost, and access, which warrant careful discussion.
Review • Journal • IO biomarker
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
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Yescarta (axicabtagene ciloleucel) • Breyanzi (lisocabtagene maraleucel) • Kymriah (tisagenlecleucel-T)
1m
Long-term Follow up Local Registry Study of Kymriah in South Korea (clinicaltrials.gov)
P=N/A, N=179, Recruiting, Novartis Pharmaceuticals | N=500 --> 179
Enrollment change
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Kymriah (tisagenlecleucel-T)
2ms
Five-Year Analysis of the JULIET Trial of Tisagenlecleucel in Patients With Relapsed/Refractory Large B-Cell Lymphoma. (PubMed, J Clin Oncol)
No new safety signals or secondary T-cell malignancies were reported. These findings continue to support the curative potential of tisagenlecleucel in a subset of patients with r/r LBCL.
Journal
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CRP (C-reactive protein)
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Kymriah (tisagenlecleucel-T)
3ms
Exploring CD19-targeted Immunotherapy Strategies for Human B-cell Lymphoma. (PubMed, Arch Razi Inst)
There are several FDA-approved anti-CD19 CAR-T cells, including Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel, as well as anti-CD19 monoclonal antibodies (mABs), such as loncastuximab tesirine and tafasitamab...Blinatumomab, the inaugural FDA-approved antibody to be produced using BiTE technology, has demonstrated notable benefits in clinical trials investigating its use in the treatment of B-cell acute lymphoblastic leukemia (B-ALL)...Furthermore, we engaged in a discourse on the various treatment options concerning CD19 targeting, accompanied by an exposition of the pertinent clinical studies. In this regard, the efficacy, safety, and limitations of each option were thoroughly delineated.
Review • Journal
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CD20 (Membrane Spanning 4-Domains A1) • TNFRSF8 (TNF Receptor Superfamily Member 8) • CD79B (CD79b Molecule) • CD52 (CD52 Molecule)
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Blincyto (blinatumomab) • Yescarta (axicabtagene ciloleucel) • Breyanzi (lisocabtagene maraleucel) • Kymriah (tisagenlecleucel-T) • Zynlonta (loncastuximab tesirine-lpyl) • Monjuvi (tafasitamab-cxix)
3ms
Clinical Impact of LAG3 Single-Nucleotide Polymorphism in DLBCL Treated with CAR-T Cell Therapy. (PubMed, Int J Mol Sci)
LAG3 rs870849 may affect treatment outcome in CAR-T cell therapy, with favorable outcomes in T455 carriers. Specific combinations of CTLA4 and LAG3 germline variants may cooperate to affect the response to CAR-T cell therapy.
Journal • IO biomarker
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LAG3 (Lymphocyte Activating 3)
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Yescarta (axicabtagene ciloleucel) • Breyanzi (lisocabtagene maraleucel) • Kymriah (tisagenlecleucel-T)
3ms
Relapsed/Refractory Large B-cell Lymphoma With NT-I7 Post-CD19 CAR T-cell Therapy (clinicaltrials.gov)
P1, N=17, Completed, NeoImmuneTech | Recruiting --> Completed | N=57 --> 17 | Trial completion date: Feb 2026 --> Mar 2025
Trial completion • Enrollment change • Trial completion date
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Yescarta (axicabtagene ciloleucel) • Breyanzi (lisocabtagene maraleucel) • Kymriah (tisagenlecleucel-T) • Hyleukin-7 (efineptakin alfa)