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DRUG:

Kymriah (tisagenlecleucel-T)

i
Other names: CART 19, CTL019, 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, CART-19, anti-CD19-CAR retroviral vector-transduced autologous T cells, CTL-019, Tisa-cel
Company:
Novartis, University of Pennsylvania
Drug class:
CD19-targeted CAR-T immunotherapy
Related drugs:
1d
LOKI: Optimizing Lymphodepletion to Improve Outcomes in Patients Receiving Cell Therapy With Kymriah (clinicaltrials.gov)
P1, N=0, Withdrawn, University Health Network, Toronto | N=40 --> 0 | Recruiting --> Withdrawn
Enrollment change • Trial withdrawal
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cyclophosphamide • Kymriah (tisagenlecleucel-T) • fludarabine IV
22d
Trial completion date
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Rituxan (rituximab) • lenalidomide • doxorubicin hydrochloride • cyclophosphamide • vincristine • prednisone • Kymriah (tisagenlecleucel-T)
1m
Addition of nivolumab tailored by expansion of CAR-T cells in patients with stable/progressive large B cell lymphoma at lymphodepletion - a phase 2, prospective interventional study. (PubMed, Transplant Cell Ther)
We conclude that the addition of nivolumab based on CAR-T cell expansion in patients with SD/PD-LBCL is safe and yields promising early response rates.
P2 data • Journal • CAR T-Cell Therapy • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD27 (CD27 Molecule)
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PD-1 expression
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Opdivo (nivolumab) • Yescarta (axicabtagene ciloleucel) • Kymriah (tisagenlecleucel-T)
2ms
Functional Activity of Cytokine-Induced Killer Cells Enhanced by CAR-CD19 Modification or by Soluble Bispecific Antibody Blinatumomab. (PubMed, Antibodies (Basel))
CAR-MNZ bearing the CD28-OX40-CD3ζ signaling modules, and CAR-BG2, designed on the Tisagenlecleucel CAR sequence (Kymriah®), carrying the 4-1BB and CD3ζ signaling elements, were employed. CIK + Blina displayed strongest NFAT and IFN-ɣ induction, whereas CARCIK-BG2 demonstrated superior synapse formation. All the effectors have shown therapeutic activity in vivo against the CD19+ Daudi tumor model, with CARCIK cells showing a more durable response compared to CIK + Blina, likely due to the short half-life of Blina in this model.
Journal
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CD19 (CD19 Molecule) • IL2 (Interleukin 2)
|
CD19 expression
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Blincyto (blinatumomab) • Kymriah (tisagenlecleucel-T)
2ms
Tisagenlecleucel in Primary CNS Lymphoma (clinicaltrials.gov)
P1, N=6, Completed, Matthew J. Frigault, M.D. | Active, not recruiting --> Completed
Trial completion
|
Kymriah (tisagenlecleucel-T)
3ms
Novel prognostic scoring systems for severe CRS and ICANS after anti-CD19 CAR T cells in large B-cell lymphoma. (PubMed, J Hematol Oncol)
Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel.
Journal • CAR T-Cell Therapy
|
CRP (C-reactive protein)
|
Yescarta (axicabtagene ciloleucel) • Kymriah (tisagenlecleucel-T)
4ms
The Kinetics of Inflammation-Related Proteins and Cytokines in Children Undergoing CAR-T Cell Therapy-Are They Biomarkers of Therapy-Related Toxicities? (PubMed, Biomedicines)
This study was a prospective analysis of proinflammatory proteins and cytokines in children treated with tisagenlecleucel...None of the toxicities were fatal. All of the analyzed biomarkers rose within 14 days after CAR-T infusion, with most reaching their maximum around the third day following the procedure.
Journal • CAR T-Cell Therapy • IO biomarker
|
IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL10 (Interleukin 10) • CRP (C-reactive protein)
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Kymriah (tisagenlecleucel-T)
4ms
CASSIOPEIA: Study of Efficacy and Safety of Tisagenlecleucel in HR B-ALL EOC MRD Positive Patients (clinicaltrials.gov)
P2, N=121, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting
Enrollment closed • Minimal residual disease
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CD19 (CD19 Molecule)
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Kymriah (tisagenlecleucel-T)
5ms
Activated CD4+ T Cell Proportion in the Peripheral Blood Correlates with the Duration of Cytokine Release Syndrome and Predicts Clinical Outcome after Chimeric Antigen Receptor T Cell Therapy. (PubMed, Intern Med)
Conclusion These results suggest that the proportion of activated CD4+ T cells on day 7 after tisa-cel infusion correlates with the CRS duration and predicts clinical outcomes after CAR T cell therapy. Further studies with a larger number of patients are required to validate these observations.
Clinical data • Retrospective data • Journal • CAR T-Cell Therapy
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IL2RA (Interleukin 2 receptor, alpha) • CD4 (CD4 Molecule) • IL7R (Interleukin 7 Receptor) • ISG20 (Interferon Stimulated Exonuclease Gene 20)
|
Kymriah (tisagenlecleucel-T)
5ms
Malnutrition and cachexia are associated with poor CAR T-cell therapy outcomes including survival. (PubMed, Clin Nutr ESPEN)
Pre-treatment malnutrition and cachexia was significantly associated with adverse CAR T patient outcomes, including mGPS cachexia status independently associated with inferior overall survival. Further research in this novel space is essential to confirm the extent and impact of nutritional issues, to assist with implementing dietetic pathways, and to identify potential interventions with a view to optimising outcomes.
Journal • CAR T-Cell Therapy
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CRP (C-reactive protein)
|
Yescarta (axicabtagene ciloleucel) • Kymriah (tisagenlecleucel-T)
5ms
LOKI: Optimizing Lymphodepletion to Improve Outcomes in Patients Receiving Cell Therapy With Kymriah (clinicaltrials.gov)
P1, N=40, Recruiting, University Health Network, Toronto | Not yet recruiting --> Recruiting
Enrollment open • CAR T-Cell Therapy
|
cyclophosphamide • Kymriah (tisagenlecleucel-T) • fludarabine IV
6ms
Autologous CD22 CAR T Cells Following Commercial CD19 CAR T Cells in B Cell Malignancies (clinicaltrials.gov)
P1, N=20, Recruiting, Stanford University | Not yet recruiting --> Recruiting
Enrollment open
|
CD22 (CD22 Molecule)
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Kymriah (tisagenlecleucel-T) • firicabtagene autoleucel (CRG-022)
6ms
New P1 trial • CAR T-Cell Therapy
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CD22 (CD22 Molecule)
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Kymriah (tisagenlecleucel-T) • firicabtagene autoleucel (CRG-022)
7ms
Efficacy and safety of bendamustine for lymphodepletion before lisocabtagene maraleucel. (PubMed, J Hematol Oncol)
Bendamustine has been retrospectively shown to be an effective and safe lymphodepletion regimen prior to the anti-CD19 chimeric antigen receptor T cell (CART) products tisagenlecleucel and axicabtagene ciloleucel, as well as the anti-BCMA CART products idecabtagene vicleucel and ciltacabtagene autoleucel. Neutropenia ≥ grade 3 was observed in 29.0% of patients; thrombocytopenia ≥ grade 3 occurred in 9.7%. In conclusion, bendamustine lymphodepletion before liso-cel appears to be a strategy that can drive tumor responses while ensuring a mild toxicity profile.
Journal
|
CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
|
Yescarta (axicabtagene ciloleucel) • Breyanzi (lisocabtagene maraleucel) • Kymriah (tisagenlecleucel-T) • bendamustine • Abecma (idecabtagene vicleucel) • Carvykti (ciltacabtagene autoleucel)
7ms
Early CAR- CD4+ T-lymphocytes recovery following CAR-T cell infusion: A worse outcome in diffuse large B cell lymphoma. (PubMed, EJHaem)
Among possible determinants of CD4+ T cell recovery, we recognized infusion of a 4-1BB product (tisagenlecleucel, TSA) in comparison with a CD28 (axicabtagene/brexucabtagene, AXI/BRX) (hazard ratio [HR] [95% CI]: 5.79 [1.16-24.12] p = 0.016). We conclude that a faster CAR- CD4+ T cell recovery is associated with TSA as compared to AXI/BRX. Month-1 CAR- CD4+ T cell subset recovery could represent a "red flag" for CAR-T cell therapy failure in DLBCL patients.
Journal • CAR T-Cell Therapy
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CD4 (CD4 Molecule)
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Yescarta (axicabtagene ciloleucel) • Kymriah (tisagenlecleucel-T) • Tecartus (brexucabtagene autoleucel)
7ms
Tisagenlecleucel In Primary CNS Lymphoma (clinicaltrials.gov)
P1, N=6, Active, not recruiting, Matthew J. Frigault, M.D. | Recruiting --> Active, not recruiting | Trial completion date: Nov 2022 --> Dec 2024
Enrollment closed • Trial completion date
|
Kymriah (tisagenlecleucel-T)
7ms
Testing Drug Treatments After CAR T-cell Therapy in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (clinicaltrials.gov)
P2, N=396, Recruiting, SWOG Cancer Research Network | Trial primary completion date: Dec 2024 --> Dec 2025
Trial primary completion date • CAR T-Cell Therapy
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cyclophosphamide • Yescarta (axicabtagene ciloleucel) • Breyanzi (lisocabtagene maraleucel) • Kymriah (tisagenlecleucel-T) • fludarabine IV • Polivy (polatuzumab vedotin-piiq) • Lunsumio (mosunetuzumab-axgb)
8ms
B-cell-directed CAR-T cell therapy activates CD8+ cytotoxic CARneg bystander T-cells in non-human primates and patients. (PubMed, Blood)
A transcriptionally similar population was identified in patients following Tisagenlecleucel infusion...In vitro activated and patient-derived T-cells with the bystander phenotype efficiently killed leukemic cells through a TCR-independent mechanism. Collectively, this dataset provides the first comprehensive identification and profiling of CARneg bystander CD8+ T-cells following B-cell targeting CAR-T cell therapy and suggests a novel mechanism through which CAR-T cell infusion might trigger enhanced anti-leukemic responses.
Journal • CAR T-Cell Therapy • IO biomarker
|
CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • IL2 (Interleukin 2) • KIR3DL2 (Killer Cell Immunoglobulin Like Receptor Three Ig Domains And Long Cytoplasmic Tail 2) • IL15 (Interleukin 15) • KLRD1 (Killer Cell Lectin Like Receptor D1)
|
Kymriah (tisagenlecleucel-T)
8ms
MT2017-45: CAR-T Cell Therapy for Heme Malignancies (clinicaltrials.gov)
P=N/A, N=144, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Recruiting --> Active, not recruiting | N=240 --> 144 | Trial primary completion date: Jun 2028 --> Feb 2024
Enrollment closed • Enrollment change • Trial primary completion date • CAR T-Cell Therapy
|
CD19 (CD19 Molecule)
|
CD19 expression
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cyclophosphamide • Yescarta (axicabtagene ciloleucel) • Breyanzi (lisocabtagene maraleucel) • Kymriah (tisagenlecleucel-T) • fludarabine IV • Tecartus (brexucabtagene autoleucel) • Abecma (idecabtagene vicleucel)
8ms
LOKI: Optimizing Lymphodepletion to Improve Outcomes in Patients Receiving Cell Therapy With Kymriah (clinicaltrials.gov)
P1, N=40, Not yet recruiting, University Health Network, Toronto | Initiation date: Dec 2023 --> Apr 2024
Trial initiation date • CAR T-Cell Therapy
|
cyclophosphamide • Kymriah (tisagenlecleucel-T) • fludarabine IV
9ms
Relapsed/Refractory Large B-cell Lymphoma With NT-I7 Post-CD19 CAR T-cell Therapy (clinicaltrials.gov)
P1, N=57, Recruiting, NeoImmuneTech | Phase classification: P1b --> P1
Phase classification
|
Yescarta (axicabtagene ciloleucel) • Breyanzi (lisocabtagene maraleucel) • Kymriah (tisagenlecleucel-T) • Hyleukin-7 (efineptakin alfa)
9ms
New trial
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Yescarta (axicabtagene ciloleucel) • Kymriah (tisagenlecleucel-T)
9ms
Study of Out of Specification for Tisagenlecleucel (clinicaltrials.gov)
P3, N=200, Recruiting, Novartis Pharmaceuticals | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Dec 2023 --> Apr 2025
Trial completion date • Trial primary completion date
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Kymriah (tisagenlecleucel-T)
9ms
An anti-CD19/CTLA-4 switch improves efficacy and selectivity of CAR T cells targeting CD80/86-upregulated DLBCL. (PubMed, Cell Rep Med)
We identify an upregulation of CD80 and/or CD86 in tumor tissue of (r/r) diffuse large B cell lymphoma (DLBCL) patients treated with tisagenlecleucel...In addition, immunocompetent mice show an intact CD80-CD19+ B cell population after CAR/CCR T cell treatment. The results reveal the CAR/CCR design as a promising strategy for further translational study.
Journal • CAR T-Cell Therapy
|
CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule)
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CTLA4 expression
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Kymriah (tisagenlecleucel-T)
9ms
Decoding the mechanisms of chimeric antigen receptor (CAR) T cell-mediated killing of tumors: insights from granzyme and Fas inhibition. (PubMed, Cell Death Dis)
We realized the translational relevance of these findings by examining the scRNA-seq profiles of Tisa-cel and Axi-cel infusion products and show a significant correlation between GZMB and GZMA expression at the single-cell level in a T cell subset-dependent manner. Our findings highlight the importance of the redundancy in killing mechanisms of CAR T cells and how this redundancy is important for efficacious T cells.
Journal
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FASLG (Fas ligand) • GZMB (Granzyme B) • GZMA (Granzyme A)
|
Yescarta (axicabtagene ciloleucel) • Kymriah (tisagenlecleucel-T)
10ms
Effectiveness and Safety of Tisagenlecleucel Therapy in Brazilian Patients With B-lymphocyte Malignancies (clinicaltrials.gov)
P=N/A, N=200, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting
Enrollment open
|
Kymriah (tisagenlecleucel-T)
10ms
Durable Response After Tisagenlecleucel in Adults With Relapsed/Refractory Follicular Lymphoma: ELARA Trial Update. (PubMed, Blood)
Low levels of tumor-infiltrating LAG3+CD3+ exhausted T-cells and higher baseline levels of naïve CD8+ T-cells were associated with improved outcomes. Tisagenlecleucel continued to demonstrate highly durable efficacy and a favorable safety profile in this extended follow-up of 29 months in patients with r/r FL enrolled in ELARA.
Journal • IO biomarker
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CD8 (cluster of differentiation 8) • LAG3 (Lymphocyte Activating 3)
|
Kymriah (tisagenlecleucel-T)
11ms
Trial completion date • Trial primary completion date
|
CD19 (CD19 Molecule) • IFNG (Interferon, gamma)
|
CD19 expression
|
Kymriah (tisagenlecleucel-T)
11ms
Orphan Indications for CD19 Redirected Autologous T Cells (clinicaltrials.gov)
P2, N=81, Recruiting, Stephan Grupp MD PhD | Trial primary completion date: Mar 2025 --> Mar 2028
Trial primary completion date
|
CD19 (CD19 Molecule) • KMT2A (Lysine Methyltransferase 2A)
|
MLL rearrangement • CD19 expression
|
Kymriah (tisagenlecleucel-T)
11ms
Contemporary Treatment Options Beyond Chimeric Antigen Receptor (CAR) T-Cell Therapies for Patients with Relapsed or Refractory Large B-Cell Lymphoma (LBCL): A Systematic Literature Review (SLR) (TCT-ASTCT-CIBMTR 2024)
We performed an SLR to understand the efficacy and real-world (RW) effectiveness of non–CAR T-cell therapies for R/R LBCL including tafasitamab with lenalidomide (tafa/len), polatuzumab with bendamustine/rituximab (pola-BR), loncastuximab, selinexor, epcoritamab, and glofitamab. Currently, the evidence base, particularly RW studies, for non–CAR T-cell R/R LBCL therapies is still limited. In comparison, 78 RW CAR T-cell therapy studies were published (Jacobson et al. Tandem Meeting.
Clinical • Review
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Rituxan (rituximab) • lenalidomide • Xpovio (selinexor) • Kymriah (tisagenlecleucel-T) • bendamustine • Epkinly (epcoritamab-bysp) • Zynlonta (loncastuximab tesirine-lpyl) • Monjuvi (tafasitamab-cxix) • Polivy (polatuzumab vedotin-piiq) • Columvi (glofitamab-gxbm)
11ms
Medicare Utilization and Cost Trends for CAR-T Cell Therapies in the Treatment of Large B-Cell Lymphoma (TCT-ASTCT-CIBMTR 2024)
We analyzed Medicare FFS claims data, focusing on the utilization patterns across three CAR-T products—Breyanzi, Kymriah, and Yescarta – which are indicated for the treatment of LBCL. CAR-T therapy for the treatment of LBCL has become more common within the Medicare population, primarily in the inpatient setting. This study helps understand providers' cost and associated patient care around CAR-T administration. The data shows that the average cost received by hospitals encompasses the expenses related to both the CAR-T drug and the medical services delivered to patients.
Reimbursement • US reimbursement • CAR T-Cell Therapy • Medicare
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Yescarta (axicabtagene ciloleucel) • Breyanzi (lisocabtagene maraleucel) • Kymriah (tisagenlecleucel-T)
11ms
BostonGene Announces Ten Presentations at the 65th American Society of Hematology Annual Meeting & Exposition (Businesswire)
"BostonGene...announced the selection of four abstracts for oral presentation, four abstracts as poster presentations, and two abstracts for online publication at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition being held December 9-12, 2023, in San Diego, California and virtually....This presentation highlights results from the Phase 2 ELARA trial that show efficacy, safety, pharmacokinetic, and exploratory biomarker analyses in relapsed/refractory follicular lymphoma patients treated with tisagenlecleucel after a median follow-up of more than 3 years."
P2 data
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Kymriah (tisagenlecleucel-T)
11ms
Clinical Outcomes of Patients with Relapsed/Refractory Follicular Lymphoma Treated with Tisagenlecleucel: Phase 2 Elara 3-Year Follow-up (TCT-ASTCT-CIBMTR 2024)
Pts with r/r FL maintained a high rate of durable responses more than 3 y after tisagenlecleucel infusion, including pts in high-risk subgroups such as POD24. Tisagenlecleucel's safety profile remains favorable with no new safety signals during extended follow-up. Correlative analyses suggest higher baseline levels of CD8+ naive T cells (>2.14%) are associated with improved long-term clinical outcomes.
Clinical • Clinical data • P2 data
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CD8 (cluster of differentiation 8)
|
Kymriah (tisagenlecleucel-T)
11ms
Study of Out of Specification for Tisagenlecleucel (clinicaltrials.gov)
P3, N=200, Recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2023 --> Apr 2024
Trial completion date
|
Kymriah (tisagenlecleucel-T)
12ms
An Economic Model to Estimate Costs of Cytokine Release Syndrome and Neurological Events Among Patients Treated with CAR T Cell Therapies for Relapsed or Refractory Follicular Lymphoma (ASH 2023)
This economic analysis revealed lower overall per-patient weighted average costs associated with liso-cel compared with axi-cel and tisa-cel, primarily due to lower CRS and NE rates versus axi-cel and lower NE rates versus tisa-cel. In comparison with axi-cel and tisa-cel, liso-cel demonstrated robust economic and clinical value, with lower rates of CRS and/or NEs associated with substantial cost savings per AE event.
Clinical • CAR T-Cell Therapy
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Yescarta (axicabtagene ciloleucel) • Breyanzi (lisocabtagene maraleucel) • Kymriah (tisagenlecleucel-T)
12ms
Introduction of Glofitamab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) after ≥2 Lines of Systemic Therapy Results in Cost Savings to the Healthcare System Based on a United States Budget Impact Analysis (ASH 2023)
Comparators were axicabtagene ciloleucel (Axi-cel), lisocabtagene maraleucel (Liso-cel), tisagenlecleucel (Tisa-cel), loncastuximab tesirine (Lonca), polatuzumab vedotin + bendamustine + rituximab (Pola-BR), rituximab + gemcitabine + oxaliplatin (R-GemOx), tafasitamab + lenalidomide, and epcoritamab. Over 3 years, the estimated cumulative per-patient cost of glofitamab is projected to be the lowest when compared with per-patient costs of other available T-cell engaging therapies, resulting in cost savings after its formulary adoption for the treatment of R/R DLBCL after ≥2 lines of therapy.
HEOR
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gemcitabine • Rituxan (rituximab) • lenalidomide • oxaliplatin • Yescarta (axicabtagene ciloleucel) • Breyanzi (lisocabtagene maraleucel) • Kymriah (tisagenlecleucel-T) • bendamustine • Epkinly (epcoritamab-bysp) • Zynlonta (loncastuximab tesirine-lpyl) • Monjuvi (tafasitamab-cxix) • Polivy (polatuzumab vedotin-piiq) • Columvi (glofitamab-gxbm)
12ms
The Outcome of Tisagenlecleucel (Tisa-Cel) Vs Axicabtagene Ciloleucel (Axi-Cel) CD-19 CAR-T Cell Therapy in Relapsed/Refractory NHL, Real World Data, Single Institution Experience (ASH 2023)
The cure rate with first line of therapy (R-CHOP) reaches up to 70%...All patients received lymphodepletion (LD) therapy with fludarabine and cyclophosphamide (Flu/Cy)...Tocilizumab was used in 72...Dexamethasone (Dexa) was used in CRS in 36... In this single-center retrospective analysis of CAR T-cell therapy in relapsed or refractory NHL or FL in adults, the rates of durable responses were like the real-world data. The best response rate was higher in Axi-Cel group; however, the follow-up duration of disease response is shorter in Axi-Cel group. The toxicity profile is similar in both groups with a bit higher of Grade-III-IV ICANS in Tica-Cel group.
Clinical • CAR T-Cell Therapy • Real-world evidence • Real-world
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CD19 (CD19 Molecule)
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CD19 expression
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Rituxan (rituximab) • cyclophosphamide • Yescarta (axicabtagene ciloleucel) • dexamethasone • Kymriah (tisagenlecleucel-T) • fludarabine IV • Actemra IV (tocilizumab)
12ms
The Impact of Leukapheresis Collection on Patients Undergoing Chimeric Antigen T-Cell Receptor Therapy with Tisagenlecleucel (ASH 2023)
A significant positive correlation was observed between ALC and the CD3+ cells as well as its percentage from leukapheresis for pediatric and adult patients undergoing tisagenlecleucel CAR-T. However, no significant effects were found when detecting the association between ALC with OS or EFS. In addition, there were no significant findings between IFNγ and the duration of CRS or ICANS.
Clinical
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IFNG (Interferon, gamma)
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Kymriah (tisagenlecleucel-T)
12ms
Breaking Barriers in B-Acute Lymphoblastic Leukemia Treatment: Experience of a Tertiary Hospital with the Use of a Tandem Dual CAR-T 19/22 in Pediatric & AYA Patients (ASH 2023)
Introduction Anti-CD19 chimeric antigen receptor (CAR) autologous T-cell therapy tisagenlecleucel (CTL019) has shown efficacy in pivotal trials and real-world data in relapsed/refractory pediatric B-cell precursor acute lymphoblastic leukemia (r/r B-ALL)...5%), using inotuzumab in 1 patient...5%) consisted on fludarabine 30 mg/m2/day for 4 days and cyclophosphamide 600 mg/m2/day for 2 days...Our experience suggests the efficacy of its use as a bridge to consolidative HSCT. Nevertheless, a larger number of patients in the context of a clinical trial would be necessary.
Clinical
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CD19 (CD19 Molecule) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • IL15 (Interleukin 15) • IL7 (Interleukin 7)
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CD19 expression
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cyclophosphamide • Besponsa (inotuzumab ozogamicin) • Kymriah (tisagenlecleucel-T) • fludarabine IV
12ms
CAR-T Cell Therapy in Patients with Refractory Systemic Autoimmune Diseases Exhibits Less Inflammation, Toxicities and Different Cellular Dynamics Compared to Patients with B Cell Lymphoma (ASH 2023)
All patients were treated in our center with either commercial CAR-T cell products (Axicabtagenee ciloleucel, Tisagenlecleucel, Lisocabtagen maraleucel) or with the investigational medicinal product MB-CART19...Consistent with reduced toxicity, AID patients received less tocilizumab and glucocorticoid treatment...Taken together, we observed less toxicities and severe adverse events in AID patients than in NHL patients despite similar CAR-T cell expansion and dynamics. The lack of CAR-T cell persistence and the early recurrence of B cells in AID patients is so far not explained and could provide novel insights in the biological processes controlling long-term CAR-T cell persistence.
Clinical • CAR T-Cell Therapy • IO biomarker
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CRP (C-reactive protein)
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Yescarta (axicabtagene ciloleucel) • Kymriah (tisagenlecleucel-T) • Actemra IV (tocilizumab)
12ms
Phase 2 Study of CD19 CAR T Cells with a Fully Human Binder for Large B-Cell Lymphoma in Relapse or Progression after a Murine Binder-Bearing CD19 CAR T-Cell Therapy (ASH 2023)
Pts received lymphodepletion (LD) with cyclophosphamide 300 mg/m2/d and fludarabine 30 mg/m2/d for 3 days...Prior CD19 CAR T-cell product type was lisocabtagene maraleucel, n=4 (50%); axicabtagene ciloleucel, n= 3 (37%); or tisagenlecleucel, n=1...CONCLUSIONIn LBCL pts with disease relapse or progression after a first CD19 CAR T-cell therapy, we observed low response rates and lack of durable responses after treatment with the fully human scFv-bearing product JCAR021, prompting early study termination. Lower CAR T-cell expansion during manufacturing in CAR-exposed pts suggest pre-existing T-cell dysfunction as a potential mechanism of failure.
P2 data • Preclinical • CAR T-Cell Therapy
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CD8 (cluster of differentiation 8)
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LDH elevation • CD19 positive
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cyclophosphamide • Yescarta (axicabtagene ciloleucel) • Breyanzi (lisocabtagene maraleucel) • Kymriah (tisagenlecleucel-T) • fludarabine IV
12ms
A Systematic Literature Review (SLR) and Meta-Analysis of Clinical Evidence of Second Line or Later (2L+) Treatments for Follicular Lymphoma (FL) in Adult Patients (ASH 2023)
Eligible treatments included CAR T cell therapies (axicabtagene ciloleucel, lisocabtagene maraleucel, and tisagenlecleucel), T cell engagers (mosunetuzumab, glofitamab, epcoritamab, odronextamab), phosphatidylinositol 3-kinase (PI3K) inhibitors (copanlisib, duvelisib, idelalisib), HSCT, yttrium-90 (90Y) ibritumomab tiuxetan, tazemetostat, and conventional therapies (immunochemotherapies, single- or multiagent chemo- or immunotherapies, and alkylating agents). This SLR demonstrated an evolving FL treatment landscape, with new agents such as CAR T cell therapies and T cell engagers exhibiting potential for improving effectiveness of treatment for patients in 3L+, 4L+, and 2L+ POD24 populations.
Retrospective data • Review
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Aliqopa (copanlisib) • Zydelig (idelalisib) • Copiktra (duvelisib) • Yescarta (axicabtagene ciloleucel) • Breyanzi (lisocabtagene maraleucel) • Tazverik (tazemetostat) • Kymriah (tisagenlecleucel-T) • Epkinly (epcoritamab-bysp) • Zevalin (ibritumomab tiuxetan) • Lunsumio (mosunetuzumab-axgb) • Columvi (glofitamab-gxbm) • Ordspono (odronextamab)