- |||||||||| birinapant (IGM-9427) / IGM Biosciences, emricasan (IDN 6556) / Histogen, Amerimmune
Journal: Primary cilia suppress Ripk3-mediated necroptosis. (Pubmed Central) - Dec 4, 2022
Cell death could be enhanced and shifted toward necroptosis by the caspase inhibitor emricasan, which could be blocked by inhibitors of Ripk1 and Ripk3...Moreover, loss of Nphp1, the most frequent cause of NPH, further increased susceptibility to necroptosis in non-ciliated epithelial cells, suggesting that necroptosis might contribute to the pathogenesis of the disease. Together, these data provide a link between cilia-related signaling and cell death responses and shed new light on the disease pathogenesis of NPH-related ciliopathies.
- |||||||||| birinapant (IGM-9427) / IGM Biosciences
Journal, CAR T-Cell Therapy, Heterogeneity: The IAP antagonist birinapant enhances chimeric antigen receptor T cell therapy for glioblastoma by overcoming antigen heterogeneity. (Pubmed Central) - Dec 3, 2022
In addition, birinapant could promote the activation of NF-κB signaling pathways in antigen-stimulated CAR T cells, and with a birinapant-resistant tumor model we showed that birinapant had no deleterious effect on CAR T cell functions in vitro and in vivo. Overall, we demonstrated the potential of combining the IAP antagonist birinapant with CAR T cells as a novel and feasible approach to overcoming tumor antigen heterogeneity and enhancing CAR T cell therapy for GBM.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Anti-CD 19 CAR-T Cell Therapy with Tisagenlecleucel for Ritcher Syndrome () - Nov 29, 2022 - Abstract #ASH2022ASH_7826;
She received high dose chemotherapy with R-BEAM followed by autologous stem cell transplant, followed by 4 cycles of maintenance brentuximab given every 3 weeks for her CD30 positive large B cell lymphoma...Treatment was complicated by grade 1-2 cytokine release syndrome (CRS) (treated with tocilizumab and dexamethasone) requiring brief hospitalization...Venetoclax was added to ibrutinib and later, 2 cycles of Obinutuzumab were also given...She received 6 cycles of RCHOP in addition to venetoclax/ibrutinib but end of treatment PET showed disease progression...She received lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by CAR-T cell infusion with tis-cel 3.7 x 10^8 cells anti CD19 CAR-T cells on 6/7/21...She continues to be in CR now 1 year since her CAR-T cell infusion.Conclusion CAR-T cell therapy with Tisagenlecleucel shows promising activity in patients with RS. It is an evolving treatment strategy and more follow up is needed to assess the durability of the responses observed in these patients.
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
Severe Persistent Cytopenias Following CAR T-Cell Therapy in Patients with Large B-Cell Lymphoma () - Nov 29, 2022 - Abstract #ASH2022ASH_7816;
Interestingly, elevated inflammatory cytokines at day 0 (measured before infusion), such as IL10 and TNFα were associated with the development of thrombocytopenia (p = 0.027 and p = 0.023, respectively).CONCLUSIONSevere cytopenias following CD19-CAR-T are common in the real-world setting, with an estimated incidence of 25% and 80% incidence of profound thrombocytopenia and neutropenia, respectively. Our data suggest that clinical features, baseline counts, and the inflammatory profile before infusion are important determinants of cytopenia risk in CAR-T recipients.
- |||||||||| Late Infections in Patients Receiving Chimeric Antigen Receptor T Cell Therapy: Real World Retrospective Experience Form a Single Centre in United Kingdom () - Nov 29, 2022 - Abstract #ASH2022ASH_7809;
All patient received standard lymphodepletion with Fludarabine and Cyclophosphamide.Significant neutropenia was observed in majority of patients (95%) with 7.5% having persisting neutropenia beyond 12 months...The median overall survival of patients without any infections (A) was not reached while for patients with any infection (B) was 11 months (95% CI 3.8 - 18.2). The 2-year OS rates were 81.3% and 37.5% for Group A and B, respectively with p-value of 0.013 (Figure II).Conclusion :A small number of infections (mild-moderate) continued to occur after 12 months in our cohort of CAR-T patients suggesting that longer prophylaxis may be required in some patients on individualised basis.Despite the shortcomings of this study including retrospective nature and small sample size, there is suggestion of adverse outcomes in patients developing any infections following CAR-T, necessitating aggressive prophylactic approach including use of IVIg.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Tecartus (brexucabtagene autoleucel) / Gilead
CAR-T Prescriber Preferences in Adolescents and Young Adults with B-ALL () - Nov 29, 2022 - Abstract #ASH2022ASH_7812;
However, some prescribers may favor brexu-cel if there was rapid clinical decline requiring expedited turnaround time. Some changes in product preference when clinical data was presented in a blinded manner were seen, suggesting providers' willingness and feasibility to design a pragmatic study comparing tisa-cel and brexu-cel in real world practice in the AYA population.
- |||||||||| Review, Journal, CAR T-Cell Therapy: Current and Future Perspectives for Chimeric Antigen Receptor T Cells Development in Poland. (Pubmed Central) - Nov 27, 2022
In this review we present molecular pathways involved in the activation of CAR-T cells, describe in details the structures of receptors and the biological activity of CAR-T cells currently approved for clinical practice in the European Union, and explain the functional differences between them. Finally, we present the potential for the development of CAR-T cells in Poland, as well as indicate the possible directions of future research in this area, including novel modifications and applications of CAR-T cells and CAR-natural killer (NK) cells.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Journal, CAR T-Cell Therapy: Blinatumomab Prior to CAR-T Cell Therapy-A Treatment Option Worth Consideration for High Disease Burden. (Pubmed Central) - Nov 27, 2022
To conclude, blinatumomab can effectively lower disease burden with fewer side effects than standard chemotherapeutics. Therefore, it may be a valid option for patients with high-disease burden prior to CAR-T cell therapy without clear evidence of compromising efficacy; however, further investigations are necessary.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
Journal, CAR T-Cell Therapy: Host metabolome predicts the severity and onset of acute toxicities induced by CAR T-cell therapy. (Pubmed Central) - Nov 19, 2022
Lower concentration of the amino acid hydroxyproline was associated with higher grade and faster onset of ICANS, whereas low glutamine was negatively correlated with faster development of ICANS. Overall, our data indicate that the pre-treatment host metabolome has biomarker potential in determining the risk of clinically significant CRS and ICANS, and may be useful in risk stratification of patients prior to anti-CD19 CAR T-cell therapy.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
Journal: Clash of the titans: axi-cel versus tisa-cel for advanced-stage DLBCL. (Pubmed Central) - Nov 18, 2022
Overall, our data indicate that the pre-treatment host metabolome has biomarker potential in determining the risk of clinically significant CRS and ICANS, and may be useful in risk stratification of patients prior to anti-CD19 CAR T-cell therapy. No abstract available
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
Review, Journal, CAR T-Cell Therapy: Emerging Role of Autologous CD19 CAR T-Cell Therapies in the Second-Line Setting for Large B-cell Lymphoma: A Game Changer? (Pubmed Central) - Nov 18, 2022
Several differences exist between these trials, including trial designs, patient population, crossover permissibility, bridging therapy, and end-point definitions. In this review, we summarize the current evidence for the treatment of patients with LBCL in the third line and beyond and standard treatment in the second line before CAR T therapy approval and interpret outcomes of the three trials examining the role of CAR T therapy in the second line and their impact in reshaping future practice.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Clinical, Journal, HEOR: A multicenter study of ICU resource utilization in pediatric, adolescent and young adult patients post CAR-T therapy. (Pubmed Central) - Nov 16, 2022
Toxicities associated with tisagenlecleucel are generally reversible, and our findings suggest that resource utilization once admitted to the ICU may be similar among patients with ALL receiving tisagenlecleucel versus conventional chemotherapy. As centers consider improved access to care and the feasibility of tisagenlecleucel certification, our study may inform strategic planning.
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
Review, Journal, CAR T-Cell Therapy: CAR-T cell therapy for patients with hematological malignancies. A systematic review. (Pubmed Central) - Nov 15, 2022
The results of this review may be used to guide clinical practice but evidence concerning safety and efficacy of CAR-T Cell therapy for hematological malignancies is still immature to recommend its application outside of clinical trials or compassionate use context for advanced and terminal cases. It is expected the results of the referred comparative studies will provide further elements to subsidize broader application of this immunotherapy.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Journal, CAR T-Cell Therapy, IO biomarker: T-cell counts in peripheral blood at leukapheresis predict responses to subsequent CAR-T cell therapy. (Pubmed Central) - Nov 13, 2022
In total, 44 patients with relapsed or refractory (r/r) DLBCL who received tisagenlecleucel at Kyoto University Hospital were included...Moreover, higher CD3 cell counts at leukapheresis were associated with significantly higher lymphocyte counts in peripheral blood at day 7 after CAR-T cell infusion (median 860 vs. 420/μL, P = 0.021), suggesting more extensive expansion of infused CAR-T cells in vivo. In conclusion, we demonstrated that the CD3 cell count at leukapheresis predicts both expansion of CAR-T cells after infusion and outcomes of CAR-T cell therapy, and are useful for building comprehensive therapeutic strategies at the time of leukapheresis.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Journal, CAR T-Cell Therapy: Impact of poverty and neighborhood opportunity on outcomes for children treated with CD19-directed CAR T-cell therapy. (Pubmed Central) - Nov 10, 2022
P1, P1/2,
We identified patients with r/r CD19+ ALL/lymphoblastic lymphoma treated on CD19-directed CAR T-cell clinical trials or with commercial tisagenlecleucel from 2012 to 2020...Investigation of multicenter outcomes and access disparities outside of clinical-trial settings is warranted. Clinical trials: NCT01626495; NCT02435849 ; NCT02374333; NCT02228096; NCT02906371.
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
Review, Journal, CAR T-Cell Therapy: Chimeric Antigen Receptor T-Cell (CAR T-Cell) Therapy for Primary and Secondary Central Nervous System Lymphoma: A Systematic Review of Literature. (Pubmed Central) - Nov 5, 2022
However, TRANSCEND study for Lisocabtagene maraleucel in relapsed refractory large cell lymphoma allowed patients with CNS involvement and reported manageable CNS toxicities in these patients...In this systematic review, we analyzed available literature to evaluate the role of CAR T-cell therapy in both primary and secondary CNS lymphoma using Embase, Cochrane, and PubMed databases. A total of 14 studies, including 8 retrospective analyses and 6 prospective studies/clinical trials, were included in the qualitative synthesis to study the safety and efficacy of CAR T. Based on our analysis, CAR T-cell therapy appears to be associated with reasonable efficacy and a manageable safety for primary and secondary CNS lymphoma.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Journal: Essential medicines for childhood cancer in Europe: a pan-European, systematic analysis by SIOPE. (Pubmed Central) - Nov 5, 2022
Medicines that were defined as essential within this project should be available for the treatment of childhood and adolescent cancer continuously and across Europe. This list can be used to support and guide stakeholders and policy makers in negotiations on a national and European level regarding shortages, accessibility, and affordability of these medicines.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
Cytokine Release Syndrome (CRS) Is Not Required for CAR-T Cell Efficacy in Aggressive Large B-NHL (Hall D (Ernest N. Morial Convention Center)) - Nov 4, 2022 - Abstract #ASH2022ASH_6750;
Having CRS was associated with cytopenias at day 30 post infusion, though not at subsequent time points. These findings lend further support to the finding that development of CRS does not impact efficacy of CAR T-cell therapy.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
Feasibility of Patient-Reported Outcome Assessment in the Acute Phase after CAR T-Cell Therapy in Lymphoid Malignancies: A Pilot Study (Hall D (Ernest N. Morial Convention Center)) - Nov 4, 2022 - Abstract #ASH2022ASH_6729;
The rate of missing data with both PROMIS-29 and FACT-Lym was greatest at day#14 and day#21 post-CAR, which correlated with a drop in HRQoL. Notably, PROMIS-29 demonstrated significant variability in PROs in the domains of physical function, fatigue, and satisfaction with social roles, whereas only one FACT-Lym domain (functional wellbeing) showed significant variability.
|
