- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Journal, HEOR, CAR T-Cell Therapy: CAR T-cell Therapy for Diffuse Large B-cell Lymphoma in Canada: A Cost-Utility Analysis. (Pubmed Central) - Apr 3, 2024
For patients with diffuse large B-cell lymphoma who failed 2 or more lines of systemic therapy, CAR T was not found to be a cost-effective treatment option at a willingness-to-pay threshold of $100,000.These results heavily depend on the expected long-term survival. The uncertainty in the model may be improved using real-world evidence reported in the future.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Journal, CAR T-Cell Therapy, IO biomarker: B-cell-directed CAR-T cell therapy activates CD8+ cytotoxic CARneg bystander T-cells in non-human primates and patients. (Pubmed Central) - Apr 1, 2024
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.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Review, Journal, Adverse events, CAR T-Cell Therapy: Ocular adverse (Pubmed Central) - Mar 29, 2024
The systematic review resulted in 8 case reports encompassing 19 patients which included a total of 27 events. This study demonstrates the importance of anticipation of potential ocular adverse events by ophthalmologists and oncologists as they can greatly contribute to morbidity in patients with cancer.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Rituxan (rituximab) / Roche
Journal, CAR T-Cell Therapy, Real-world evidence, Real-world: Optimizing Real-World Outcomes in High-Risk Relapsed/Refractory (r/r) FL with CAR-T Cell Therapy: A Vodcast and Case Example. (Pubmed Central) - Mar 21, 2024
This study demonstrates the importance of anticipation of potential ocular adverse events by ophthalmologists and oncologists as they can greatly contribute to morbidity in patients with cancer. The patient received eight cycles of rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP), followed by irradiation and rituximab maintenance (first-line) and then received rituximab 4?
- |||||||||| Enrollment closed, Enrollment change, Trial primary completion date: MT2017-45: CAR-T Cell Therapy for Heme Malignancies (clinicaltrials.gov) - Mar 17, 2024
P=N/A, N=144, Active, not recruiting,
CAR-T cell therapy should be not withheld for elderly patients with r/r DLBCL. Recruiting --> Active, not recruiting | N=240 --> 144 | Trial primary completion date: Jun 2028 --> Feb 2024
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
Journal, CAR T-Cell Therapy: Effective sequencing of chimeric antigen receptor T-cell therapy in the treatment of LBCL in 2023. (Pubmed Central) - Mar 12, 2024
Lastly, we will turn our attention to the horizon as we explore some of the ongoing questions of how to best leverage the curative potential of CAR T-cell therapy for the most effective management of LBCL. These areas include the consideration of CAR T-cell therapy in the frontline setting, the optimal timing for CAR T-cell referral, the optimal bridging approach, and how to continue advancing novel CAR T-cell approaches in the context of the current treatment landscape.
- |||||||||| Advances in Science and Challenges at HTA: The Case of CRISPR Technologies () - Mar 8, 2024 - Abstract #ISPOR2024ISPOR_1800;
Exa-cel and subsequent CRISPR-based technologies are expected to face similar challenges to other cell and gene therapies, with the risk of off-target gene editing likely to be scrutinized for many years to come. HTA agencies may be more willing to accept uncertainty around clinical benefit for products demonstrating cost savings for healthcare systems.
- |||||||||| Cost-Effectiveness Evaluations of CAR-T Cell Therapies By Health Technology Assessment Agencies () - Mar 8, 2024 - Abstract #ISPOR2024ISPOR_1791;
Despite the high ICER associated with these therapies, the majority of the evaluations led to favorable reimbursement decisions. Nonetheless, the substantial costs linked to CAR-T therapies call for discussions on innovative financing methods for their incorporation into health systems, emphasizing the need to balance efficacy, cost, and long-term benefits in healthcare decision-making.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Targeted Literature Review of Cost-Effectiveness Models in Relapsed/Refractory Follicular Lymphoma () - Mar 8, 2024 - Abstract #ISPOR2024ISPOR_381;
A total of 66 patients (median age, 59.5 yr; range, 23 Treatments in NICE TAs (bendamustine + obinutuzumab [BO]) and CADTH reviews (axicabtagene ciloleucel, tisagenlecleucel, BO) were recommended for R/R FL in the UK and Canada, respectively, with ICERs ranging from
- |||||||||| Brukinsa (zanubrutinib) / BeiGene, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Budget Impact Analysis of Zanubrutinib + Obinutuzumab for the Treatment of Relapsed or Refractory Follicular Lymphoma in the United States () - Mar 8, 2024 - Abstract #ISPOR2024ISPOR_287;
Treatments in NICE TAs (bendamustine + obinutuzumab [BO]) and CADTH reviews (axicabtagene ciloleucel, tisagenlecleucel, BO) were recommended for R/R FL in the UK and Canada, respectively, with ICERs ranging from In the payer plan, 19 R/R FL patients were estimated to receive 3L+ treatment with ZO, lenalidomide
- |||||||||| aDC1 vaccine / Roswell Park, University of Pittsburgh
Activating anti-MDS immunity with polarized dendritic cell vaccines (Section 4) - Mar 5, 2024 - Abstract #AACR2024AACR_9441;
We hypothesized that restoration of this population using a novel DC vaccination approach - alpha-type-1 polarized dendritic cells (?DC1) - might compensate for this deficiency and restore immunity...To date, our results suggest that generation of MDS patient-derived ?DC1 cells is feasible and additional work is being performed to fully characterize their ability to activate anti-MDS immune responses. Since ?DC1s have an established safety profile in patients with solid tumors, we anticipate that we will be able to rapidly translate our results to the clinic.
- |||||||||| birinapant (IGM-9427) / IGM Biosciences
Evaluating TNF-receptor associated factor 2 (TRAF2) as a targetable driver of immune resistance in LKB1 deficient non-small cell lung cancer (Section 42) - Mar 5, 2024 - Abstract #AACR2024AACR_6563;
This showed that inhibition of cIAP1 using birinapant was synergistic to CD8 cytotoxicity, as previously known, but the synergy was much more pronounced in STK11 mutant vs STK11-WT context (Bliss index 38, P<1e-10). Together, these data demonstrate that the link between STK11-loss and cIAP1 dysregulation is likely through over-expression of TRAF2, and support the strategy of targeting TRAF2/cIAP1 to overcome immune resistance STK11-deficient NSCLC.
- |||||||||| Identifying novel therapies from unbiased screens in AML with MECOM re-arrangement (Section 29) - Mar 5, 2024 - Abstract #AACR2024AACR_5399;
Co-targeting the other identified druggable vulnerabilities from the drug screen with BETi (mTOR/PI3K with BGT-226 and dactolisib, Bcl-xL with navitoclax and A1155463, as well as CBP/p300 (with GNE781, identified through the CRISPR screen), exerted synergistic lethality in 3q26.2-r AML cells...These findings demonstrate promising preclinical activity of BETi and IAP protein or mTOR/PI3K antagonists in the cellular models of AML with EVI1 overexpression. This supports the rationale to determine in vivo efficacy of these BETi-based combinations against this therapy-resistant AML sub-type.
- |||||||||| birinapant (IGM-9427) / IGM Biosciences
Tumor-extrinsic BIRC3 promote sensitivity to checkpoint inhibition immunotherapy in breast cancer (Section 47) - Mar 5, 2024 - Abstract #AACR2024AACR_5104;
Birinapant, a selective BIRC3 inhibitor, was then used to investigate the effect of BIRC3 blockade on tumor immune microenvironment (TIME) landscape of breast cancer syngeneic mouse models by flow cytometry...Our study revealed a positively association between BIRC3 and anti-tumor immune landscape in breast cancer. Notably, we established a validated prognosis model based on BIRC3 and BIRC3 associated immunomodulators in breast cancer.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Review, Journal, HEOR, Cost-effectiveness, Cost effectiveness: Cost and cost-effectiveness of immunotherapy in childhood ALL: A systematic review. (Pubmed Central) - Feb 26, 2024
No studies have evaluated blinatumomab or inotuzumab ozogamicin...The cost-effectiveness of tisagenlecleucel was highly dependent on list price and cure rates. This study can inform the use of tisagenlecleucel in pALL.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Journal, CAR T-Cell Therapy: An anti-CD19/CTLA-4 switch improves efficacy and selectivity of CAR T (Pubmed Central) - Feb 23, 2024
In Bulgaria, Kymriah 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
- |||||||||| Hyleukin-7 (efineptakin alfa) / Genexine, NeoImmuneTech
Phase classification, CAR T-Cell Therapy: Relapsed/Refractory Large B-cell Lymphoma With NT-I7 Post-CD19 CAR T-cell Therapy (clinicaltrials.gov) - Feb 21, 2024
P1, N=57, Recruiting,
Reinfusion of CTL019/tisagenlecleucel or huCART19 is safe, may reduce relapse risk in a subset of patients, and can reinduce remission in CD19-positive relapse. Phase classification: P1b --> P1
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Trial completion date, Trial primary completion date: Study of Out of Specification for Tisagenlecleucel (clinicaltrials.gov) - Feb 15, 2024
P3, N=200, Recruiting,
Trial completion date: Oct 2025 --> Jan 2025 | Trial primary completion date: Oct 2024 --> Jan 2025 Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Dec 2023 --> Apr 2025
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
Journal, CAR T-Cell Therapy: Monocytes in leukapheresis products affect the outcome of CD19-targeted CAR T-cell therapy in lymphoma patients. (Pubmed Central) - Feb 15, 2024
Accordingly, response and progression free survival were also negatively influenced by high circulating absolute monocyte counts at the time of leukapheresis. The combined evaluation of peripheral blood monocytes at the time of leukapheresis and the four-gene signature, represents a novel tool to identify R/R LBCL patients at very high risk of progression after CAR T, and could be used to plan trials evaluating CAR T cells versus other novel treatments or allogeneic CAR T cells, but also highlights the need to incorporate monocyte depletion strategies for better CAR T production.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
TREATMENT WITH TISAGENLECLEUCEL OF RELAPSE REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA (ePoster area) - Feb 14, 2024 - Abstract #EBMT2024EBMT_2765;
In real world setting treatment with tisagenlecleucel had similar efficacy and safety as in clinical trials. Analysis of initial laboratory values could be used in real world setting to predict response to the treatment and development of complications, but further research is needed.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
THE DARK SIDE OF CORTICOSTEROIDS IN CD19.CAR-T CELL THERAPY (CLYDE) - Feb 14, 2024 - Abstract #EBMT2024EBMT_2644;
This evidence suggests that a higher cumulative corticosteroid dose after CAR-T cell infusion may have a harmful effect in OS and PFS, without compromising CAR+T cell expansion. Further analyses in larger cohorts are needed to confirm this result and to investigate the detrimental effect of steroids on CAR-T cell activity rather than quantity.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
THE DARK SIDE OF CORTICOSTEROIDS IN CD19.CAR-T CELL THERAPY (ePoster area) - Feb 14, 2024 - Abstract #EBMT2024EBMT_2643;
This evidence suggests that a higher cumulative corticosteroid dose after CAR-T cell infusion may have a harmful effect in OS and PFS, without compromising CAR+T cell expansion. Further analyses in larger cohorts are needed to confirm this result and to investigate the detrimental effect of steroids on CAR-T cell activity rather than quantity.
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
SITE-SPECIFIC RESPONSES AND EXTRANODAL INVOLVEMENT IMPLICATIONS IN LARGE B-CELL LYMPHOMAS TREATED WITH CD19-CART THERAPY (Hall 3 South) - Feb 14, 2024 - Abstract #EBMT2024EBMT_2556;
It emphasizes the necessity for tailored management strategies specific to EN involvement, advocating for organ-specific approaches in future studies. Additionally, further investigations should delve into the underlying biology driving sanctuary sites to enhance our understanding and refine therapeutic interventions.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Actemra IV (tocilizumab) / Roche, JW Pharma, Yescarta (axicabtagene ciloleucel) / Gilead
SERUM AMYLOID-A IN CAR-T CELL THERAPY: A NEW ACUTE PHASE REACTANT (ePoster area) - Feb 14, 2024 - Abstract #EBMT2024EBMT_2527;
We studied 15 consecutive patients affected by Diffuse Large B-Cell Lymphoma (DLBCL) (53.3%), transformed Follicular Lymphoma (tFL) (26.7%), and Mantle cell Lymphoma (20%), treated at our institution with axi-cel (60%), tisa-cel (20%), or brexu-cel (20%) between May and November 2023...This may be possibly biased by iron overload and the use of tocilizumab, respectively... In conclusion, SAA emerges as a valuable acute-phase protein in the setting of CAR-T cells,not only associating with CRP and procalcitonin but also outperforming other APPs in characterizing CRS.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
REAL-WORLD EXPERIENCE OF CAR T-CELL THERAPY: A SINGLE CENTRE EXPERIENCE (CLYDE) - Feb 14, 2024 - Abstract #EBMT2024EBMT_2395;
CAR-T therapy provides an answer for some, with acceptable toxicity. Our real-world data shows that over the years, with broader selection criteria, inclusion of older patients, and those with higher disease burden, worse outcomes are observed.
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