- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Tecartus (brexucabtagene autoleucel) / Gilead, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
Cost-Effectiveness Analyses (CEAs) of CAR-T Therapies Over the Past Four Years: What's New? (Virtual) - Sep 1, 2022 - Abstract #ISPOREU2022ISPOR_EU_1160;
Over the past four years, CEAs have expanded to the comparison of CAR-T therapies and further work has been conducted to better understand the CEA drivers. However, real world evidence and long-term data is needed to confirm these assessments.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Comparison of Outcomes-Based Reimbursement (OBR) Schemes in Europe and the Us for CAR-T Cell Therapy: Tisagenlecleucel (In-person; Virtual) - Sep 1, 2022 - Abstract #ISPOREU2022ISPOR_EU_539;
Payers are showing openness to different reimbursement mechanisms to enhance patient access, demonstrated by the novel OBR approaches for tisagenlecleucel in Germany, Italy and Spain. This shows promise for the future reimbursement of high-cost therapies and demonstrates payer willingness to engage in payment models if; a) the clinical need for a product is significant, and b) there are no data, legal or administrative hurdles which cannot be overcome.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
217: Poster Tour: Case Studies (In-person) - Sep 1, 2022 - Abstract #ISPOREU2022ISPOR_EU_185;
Stakeholder perspective: Industry Posters featured in this tour:HPR125: Real-World External Control Arm to Support Indication for Tisagenlecleucel in Relapsed/Refractory Follicular Lymphoma in the European Union: A Use Case HTA115: Optimizing HTA Strategies to Improve Assessment Outcomes and Reimbursement for CAR-T Therapies: A German and UK Case Study OP10: Claims Analysis During Financial Due Diligence of Aficamtem for HCM OP11: Application of Evidence Generation and Synthesis Strategies to Gain Market Access & Reimbursement, and Deliver Value: Two Case Studies PCR175: Methods for Elderly Blood Draw Participant Recruitment PCR176: Methods for Elderly Colonoscopy Naïve Participant Recruitment
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
Clinical, Clinical guideline, P3 data, CAR T-Cell Therapy: Role of CD19 CAR T Cells in Second Line Large B Cell Lymphoma: Lessons from Phase 3 Trials - An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. (Pubmed Central) - Aug 31, 2022
These three studies, while largely addressing the same question, had different outcomes with ZUMA-7 and TRANSFORM demonstrating a significant improvement with CD19 CAR T-cell therapy in second line compared to SOC, while BELINDA did not show any benefit. The US FDA has now approved axicabtagene ciloleucel for LBCL that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy. Following the reporting of these practice changing studies, a group of experts convened by the American Society for Transplantation and Cellular Therapy now provides a comprehensive review of the three studies, emphasizing potential differences, and share perspectives on what these results mean to clinical practice in this new era of treatment of B-cell lymphomas.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Journal: Robust immune responses to SARS-CoV-2 in a pediatric patient with B-Cell ALL receiving tisagenlecleucel. (Pubmed Central) - Aug 27, 2022
The T-cell response was polyfunctional and predominantly CD4 restricted. This data has important implications for the understanding of SARS-CoV-2 immunity in patients with impaired immune systems and the potential application of SARS-CoV-2-specific T-cell therapeutics to treat patients with blood cancers who receive B cell depleting therapy.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Review, Journal, CAR T-Cell Therapy: Leukapheresis guidance and best practices for optimal chimeric antigen receptor T-cell manufacturing. (Pubmed Central) - Aug 24, 2022
Challenges of obtaining optimal leukapheresis product for CAR T-cell manufacturing include vascular access for smaller patients, achieving sufficient T-cell yield, eliminating contaminating cell types in the leukapheresis product, determining appropriate washout periods for medication and managing adverse events at collection. In this review, the authors provide recommendations on navigating CAR T-cell therapy and leukapheresis based on experience and data from tisagenlecleucel manufacturing in clinical trials and the real-world setting.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Journal, CAR T-Cell Therapy: A unique hub-and-spoke model to optimize patient management in lymphoma using novel CAR-T cell therapy in southeast and south Asia. (Pubmed Central) - Aug 12, 2022
Currently, Singapore is the only country in southeast and south Asia with market authorization of the CAR-T product, tisagenlecleucel...Patient support from referring and treating physicians, critical to the success of the undertaking, is characterised by early communication, patient selection, multi-disciplinary care, post-treatment monitoring, and attention to detail. The patient journey and the development and implementation of this unique collaboration are discussed.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Journal, Real-world evidence: Real-world characteristics of T-cell apheresis and clinical response to tisagenlecleucel in B-cell lymphoma. (Pubmed Central) - Aug 12, 2022
In multivariate analysis, CD8 TN/SCM proportion and International Prognostic Index (IPI) at the time of apheresis were independent risk factors for early progression. Our data show that an easy characterization by flow cytometry of the T-cell phenotype at the time of decision to use commercial CAR-T cells can help to better select patients who will respond.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
P4 data, Journal, Adverse events, CAR T-Cell Therapy: Post-Marketing Surveillance of CAR-T-Cell Therapies: Analysis of the FDA Adverse Event Reporting System (FAERS) Database. (Pubmed Central) - Aug 12, 2022
Our data show that an easy characterization by flow cytometry of the T-cell phenotype at the time of decision to use commercial CAR-T cells can help to better select patients who will respond. Our study confirms the well-known adverse drug reactions and detects potentially emerging safety issues specific for each chimeric antigen receptor T-cell therapy, also providing insights into a stronger role for tisa-cel in inducing some immunodeficiency-related events (e.g., hypogammaglobulinemia, infections) and coagulopathies, and for axi-cel in neurotoxicity.
- |||||||||| Serial Inflammatory Cytokine Levels Are Increased in Atrial Fibrillation After Chimeric Antigen Receptor T-Cell (CAR-T) Therapy (Zone 2, Science and Technology Hall, Level 3; Poster Board no. 2062) - Aug 11, 2022 - Abstract #AHA2022AHA_4092;
This was a prospective observational cohort study involving patients diagnosed with lymphoma treated with CAR-T therapy (axicabtagene ciloleucel, tisagenlecleucel, brexucabtagene autoleucel)...Tocilizumab was given to seven patients...In the setting of CAR-T, the elevation of multiple pro-inflammatory pathways from cytokine release syndrome may be related to the adverse cardiac events, including atrial fibrillation. Further studies are needed to identify and investigate the role of specific inflammatory mediators in cardiac events after CAR-T therapy.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Journal, CAR T-Cell Therapy: Apheresis for chimeric antigen receptor T-cell production in adult lymphoma patients. (Pubmed Central) - Aug 11, 2022
Lymphapheresis with the Spectra Optia cMNC program provided a sufficient quantity of CD3-positive lymphocytes for CAR T-cell manufacturing for the majority of patients despite their heavy pretreatment and advanced age. Moreover, we are the first to advocate early pre-emptive lymphocyte collection in DLBCL-NOS patients intended to undergo treatment with Tisagenlecleucel.
- |||||||||| birinapant (IGM-9427) / IGM Biosciences
Journal: Interaction of LATS1 with SMAC links the MST2/Hippo pathway with apoptosis in an IAP-dependent manner. (Pubmed Central) - Aug 11, 2022
Finally, we show that LATS1-SMAC interaction is regulated by the SMAC mimetic Birinapant, which requires C-IAP1 inhibition and the degradation of XIAP, suggesting that the MST2 pathway is part of the mechanism of action of Birinapant. Overall, the current work shows that SMAC-dependent apoptosis is regulated by the LATS1 tumour suppressor and supports the idea that LATS1 is a signalling hub that regulates the crosstalk between the MST2 pathway, the apoptotic network and the ERK pathway.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
Preclinical, Journal, CAR T-Cell Therapy: Phenotypic composition of commercial anti-CD19 CAR-T cells affects in vivo expansion and disease response in large B-cell lymphoma patients. (Pubmed Central) - Aug 6, 2022
As the current tisagenlecleucel package insert dose-range remains broad, this work has implications in regard to targeting higher cell doses to optimize patients for long-standing remission. Our data indicate that despite the great heterogeneity of Tisa-cel and Axi-cel products, the differentiation status of the infused cells mediates CAR-T cell in vivo proliferation that is necessary for anti tumor response.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Trial termination, Combination therapy: Study of Tisagenlecleucel in Combination With Ibrutinib in r/r Diffuse Large B-cell Lymphoma Patients (clinicaltrials.gov) - Aug 5, 2022
P1, N=10, Terminated,
Our data indicate that despite the great heterogeneity of Tisa-cel and Axi-cel products, the differentiation status of the infused cells mediates CAR-T cell in vivo proliferation that is necessary for anti tumor response. Completed --> Terminated; Business reasons
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
Journal, CAR T-Cell Therapy, Real-world evidence: GLA/DRST real-world outcome analysis of CAR-T cell therapies for large B-cell lymphoma in Germany. (Pubmed Central) - Aug 3, 2022
In conclusion, this study suggests that important outcome determinants of CD19-directed CAR-T cell treatment of LBCL in the real-world setting are bridging success, CAR-T product selection, LDH, and the absence of prolonged neutropenia and/or severe neurotoxicity. These findings may have implications for designing risk-adapted CAR-T cell therapy strategies.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
Retrospective data, Journal, HEOR, CAR T-Cell Therapy, Real-world evidence: Best Treatment Option for Patients With Refractory Aggressive B-Cell Lymphoma in the CAR-T Cell Era: Real-World Evidence From GELTAMO/GETH Spanish Groups. (Pubmed Central) - Aug 3, 2022
Our results suggest that the efficacy of CAR-T cell therapy is superior to pSOC in the real-world setting. Furthermore, axi-cel could be superior in efficacy to tisa-cel, although more toxic, in this group of refractory patients according to SCHOLAR-1 criteria.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
18FDG PET/CT Parameters for the Prediction of CAR T-Cell Therapy Response among Patients with Large B-Cell Lymphoma (Henry B. Gonzalez Convention Center, Room 207) - Aug 1, 2022 - Abstract #ASTRO2022ASTRO_2098;
Bulky disease (≥ 5 cm) is associated with significantly inferior OS. These data suggest that there may be a role for pre- CAR T radiation therapy targeting bulky site(s) with high FDG avidity, regardless of symptoms, thereby reducing disease burden prior to CAR-T cell therapy, which may lead to improved efficacy and reduced CAR T-related adverse events.
- |||||||||| Radiotherapy for Relapse after Chimeric Antigen Receptor T Cell Therapy in Hematologic Malignancies (Henry B. Gonzalez Convention Center, Room 214) - Aug 1, 2022 - Abstract #ASTRO2022ASTRO_1448;
Patients received axicabtagene (n=14), lisocabtagene (n=13), tisagenlecleucel (n=9), experimental CAR T (n=4), idecabtagene (n=3), and brexucabtagene (n=1). SRT has promising and diverse utility after CAR T. Prolonged survival can be achieved with SRT bridging to allo/second CAR T or even with definitive SRT in the setting of limited relapse and when it is feasible to irradiate all active disease to a definitive dose.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
Journal, Real-world evidence: A national service for delivering CD19 CAR-Tin large B-cell lymphoma - The UK real-world experience. (Pubmed Central) - Jul 29, 2022
This prospective RW population of CAR-T eligible patients offers important insights into the clinical benefit of CD19 CAR-T in LBCL in daily practice. Our results confirm long-term efficacy in patients receiving treatment similar to the pivotal trials, but highlight the significance of early CAR-T failure.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Journal: Relative hypercoagulation induced by suppressed fibrinolysis after tisagenlecleucel infusion in malignant lymphoma. (Pubmed Central) - Jul 29, 2022
In conclusion, a hypofibrinolytic and relatively hypercoagulable state concomitant with significant total PAI-1 elevation was observed at the onset of CRS even in DLBCL patients with mild CRS. Our results will facilitate understanding of CRS-related coagulopathy and they emphasize the importance of monitoring sequential coagulation/fibrinolysis parameters during CAR-T therapy.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Journal, Real-world evidence: Real-World Use of Tisagenlecleucel in Infant Acute Lymphoblastic Leukemia. (Pubmed Central) - Jul 29, 2022
This is the largest report of tisagenlecleucel use in infant B-ALL and shows that this therapy is safe and can be effective in this population. Incorporating this novel immunotherapy into the treatment of infant B-ALL offers a promising therapy for a highly aggressive leukemia.
- |||||||||| huCART19 / Novartis, CART22 / University of Pennsylvania, SCRI-CAR19x22v2 / Seattle Children's Hospital
Dual CAR T-Cell for ALL (Level 4, Grand Ballroom G-L) - Jul 26, 2022 - Abstract #SOHO2022SOHO_52;
P1, P1/2
Quantitative PCR data demonstrated that CART22-65s and huCART19 had different peak expansions that correlated with distinct cytokine release syndrome events...Early results have demonstrated manufacturing feasibility and anti-leukemia activity; however, limited dual functionality has been observed in some products. Longer follow-up and additional studies are needed to ascertain remission durability and to further optimize dual-targeted CARs.
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