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  • ||||||||||  birinapant (IGM-9427) / IGM Biosciences
    Ph-like and IKZF1plus Features in Children with Down Syndrome and B Cell Precursor Acute Lymphoblastic Leukemia (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_4266;    
    Performing an ex-vivo drug screening with 174 drugs in early to late clinical trials on blasts of 3 IKZF1plus DS-ALL patients and on 14 controls (5 B-cell lymphoblastoid cell lines, 3 PBMCs, 3 T-cells and 3 CD34+ cells, all derived from healthy donors) we observed the efficacy of drugs known to be effective in Ph-like patients such as Birinapant, a SMAC mimetic, and HDAC inhibitors...Ph-like signature and IKZF1 deletions were associated with poor outcome, with the risk of relapse further increased for IKZF1plus patients. These alterations characterize subgroups of DS-ALL patients who need tailored therapeutic strategies.
  • ||||||||||  Poor Survival Outcomes of Checkpoint Inhibitors for B-Cell Lymphomas Relapsing after or Refractory to CAR T-Cell Therapy: A Real-World Cohort from 15 U.S. Academic Institutions (R02-R05 (Ernest N. Morial Convention Center)) -  Nov 4, 2022 - Abstract #ASH2022ASH_3563;    
    Most patients received axicabtagene ciloleucel (53%), followed by tisagenlecleucel (26%) and lisocabtagene maraleucel (19%)...Most patients received pembrolizumab (49%), followed by nivolumab (43%), and 29% received concurrent therapies with CPI, mostly other immunotherapies and lenalidomide...Significant improvement in OS in patients receiving CPI concurrently with other therapies may warrant additional study to identify potential synergistic combinations. Finally, these data confirm the dismal prognosis of patients with refractory or early relapsing lymphoma after CAR-T and a pressing need for effective therapeutic approaches.
  • ||||||||||  Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
    Late Failure of Aggressive B-Cell Lymphoma Following CAR T-Cell Therapy: A Lysa Study from the Descar-T Registry (R02-R05 (Ernest N. Morial Convention Center)) -  Nov 4, 2022 - Abstract #ASH2022ASH_3562;    
    Radiotherapy can obtain prolonged responses in selected pts with localized disease. Different biological mechanisms of relapse and sensitivity to adoptive immunotherapy could explain the later loss of response in LF subgroup of pts and should be investigated.
  • ||||||||||  Kymriah (tisagenlecleucel-T) / Novartis
    Costimulatory Domains Direct Distinct Fates of CAR T Cell Dysfunction (ENMCC - 388-390) -  Nov 4, 2022 - Abstract #ASH2022ASH_3456;    
    Single cell RNA sequencing of CAR+ T cells from a patient with diffuse large B cell lymphoma who received Kymriah, a 19/BB-based CAR T cell product, demonstrated consistent transcriptional evolution...While CD28-based CARs promote classical exhaustion programs, 41BB-based CARs drive a dysfunctional trajectory driven by re-activation of FOXO proteins. Development of strategies that can bypass both forms of failure will be critical to improving the efficacy of this platform.
  • ||||||||||  Longitudinal Patient-Reported Outcomes in Patients Receiving Chimeric Antigen Receptor (CAR) T-Cell Therapy (Hall D (Ernest N. Morial Convention Center)) -  Nov 4, 2022 - Abstract #ASH2022ASH_3176;    
    Patients receiving CAR T-cell therapy experience significant QOL impairment and physical and psychological symptom burden, which peaks 1 week after cell infusion and improves by 6 months post-infusion. Given high rates of persistent severe symptoms and clinically significant psychological distress, interventions to improve the QOL of these patients are warranted.
  • ||||||||||  Kineret (anakinra) / SOBI
    Anakinra for Treatment and Prevention of CAR-T Neurotoxicity: A Systematic Review of Evidence to Inform SIE-GITMO-Sidem Guidelines (Hall D (Ernest N. Morial Convention Center)) -  Nov 4, 2022 - Abstract #ASH2022ASH_3095;    
    Preliminary studies also tested an early adoption of Anakinra for the prevention of severe ICANS. The above systematic review confirms the need of randomized clinical trials to assess the effectiveness (grade 5 ICANS, duration of ICANS, steroid cumulative dose) of Anakinra in different patients subgroups, i.e. severe ICANS, steroid-refractory ICANS, ICANS with concurrent CRS, patients at high risk of developing ICANS (Rubin 2020).
  • ||||||||||  Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
    Comorbidities Associated with Early Mortality after CD19 CAR-T Cell Therapy (Hall D (Ernest N. Morial Convention Center)) -  Nov 4, 2022 - Abstract #ASH2022ASH_2911;    
    Pts with cardiac comorbidity, hepatic dysfunction or psychiatric disturbance had a higher 100-day NRM. Similar to other studies, the combined HCT-CI score was not predictive of NRM, but individual variables were associated with higher non-CART related toxicity.
  • ||||||||||  Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
    Predictors and Implications of Renal Injury in Large Cell Lymphoma Patients Receiving CD19 CAR T Cell Therapy (Hall D (Ernest N. Morial Convention Center)) -  Nov 4, 2022 - Abstract #ASH2022ASH_2906;    
    The association between renal injury and subsequent mortality suggests that AKI is a clinically and prognostically significant complication. The discovery that readily available biomarkers reflecting physiological reserve, disease burden, and systemic inflammation inform on renal injury risk may support personalized stratification for risk mitigation.
  • ||||||||||  Improvement in Lymphoma CAR-T Outcomes over Time in the UK – CAR-T Learning Curve or Better Bridging? (Hall D (Ernest N. Morial Convention Center)) -  Nov 4, 2022 - Abstract #ASH2022ASH_2899;    
    Methods We included 120 consecutive LBCL patients approved for treatment with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) at King's College Hospital London (KCH cohort) and split them into 2 treatment eras – Era 1 (Dec 2018 - Dec 2019), and Era 2 (Jan 2020 - Mar 2022)...Similarly, for Era 2 vs 1, we observed a lower incidence of eLDH pre-LD (50% vs 66%, p 0.004), increased use of polatuzumab- based bridging (45% vs 3%, p<0.001), fewer bridging failures (10% vs 20%, p=0.003), and a higher use of tocilizumab/steroids (77%/49% vs 60%/34% (both p<0.001)...Conclusions Our data show improvement over time in survival outcomes for LBCL patients treated with CD19 CAR-T at our center and nationally which appear to be mainly driven by improvements in bridging therapy. Incidence of high-grade CAR-T toxicities was low and seems to have further reduced with more proactive toxicity management in the recent era.
  • ||||||||||  Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
    Lymphodepleting Chemotherapy before CD19 Directed CAR T-Cell Therapy: Are 3 Days Necessary? (Hall D (Ernest N. Morial Convention Center)) -  Nov 4, 2022 - Abstract #ASH2022ASH_2517;    
    Most lymphodepleting regimens use a combination of fludarabine and cyclophosphamide (flu/cy) but there is variability between dosing and duration of therapy...Of the patients that received 3 days of LD chemo, 54.8% (n=17) were treated with axicabtagene ciloleucel (axi-cel), 11 were treated with tisagenlecleucel (tisa-cel), and 3 received lisocabtagene maraleucel (liso-cel)...In this small patient sample, there were no significant differences in CAR T-cell efficacy or toxicity with a 2-day regimen. There is need for further prospective trials to ensure appropriate dosing of chemotherapy to optimize CAR T-cell response while minimizing toxicity.
  • ||||||||||  CAR T cell therapy / Mnemo Therap
    Anti-CD19 CAR T-Cell Therapy for Patients with Richter Syndrome: A Lysa Study from the Descar-T Registry (Hall D (Ernest N. Morial Convention Center)) -  Nov 4, 2022 - Abstract #ASH2022ASH_2508;    
    CD19-targeted chimeric antigenic receptor (CAR) T-cell therapy such as axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) have been transformative for patients with relapsed/refractory DLBCL...Seven (58%) patients received chemo-immunotherapy, 7 (58%) had been exposed to ibrutinib including 5 (42%) to both ibrutinib and venetoclax...Tocilizumab was administered to 9 (75%) patients...Frequency of CAR T-cell-specific adverse events was in the range of what is observed in de novo DLBCL while severity appeared higher (Schuster et al., NEJM 2019; Neelapu et al., NEJM 2017). Larger cohort with longer follow-up and prospective trials are warranted to confirm these observations.
  • ||||||||||  Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
    CD19 CAR-T Outcomes in Patients with EBV-Positive DLBCL (Hall D (Ernest N. Morial Convention Center)) -  Nov 4, 2022 - Abstract #ASH2022ASH_2507;    
    In the EBV + cohort, the median age was 47 years (range, 20-81) and included 5 (55%) pts with DLBCL-NOS, 3 (30%) pts with transformed follicular lymphoma, and one (15%) pt with high-grade B-cell lymphoma. The median number of prior lines of therapy was 2 (range, 1-5).
  • ||||||||||  PIT565 / Novartis
    PIT565, a First-in-Class Anti-CD19, Anti-CD3, Anti-CD2 Trispecific Antibody for the Treatment of B Cell Malignancies (Hall D (Ernest N. Morial Convention Center)) -  Nov 4, 2022 - Abstract #ASH2022ASH_2197;    
    P1
    Taken together, the findings from the preclinical studies suggest that PIT565 may achieve deeper and more durable responses compared to competitor CD3 bispecifics. First-in-human trial of PIT565 (NCT05397496) has been initiated and will be conducted in patients who are diagnosed with relapsed and/or refractory adult NHL after receiving two or more lines of chemotherapy and patients with relapsed and/or refractory B-ALL.
  • ||||||||||  Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
    Inflammatory Biomarker Clusters Are Predictive of Response and Toxicity in Large B-Cell Lymphoma Treated with CD19 CAR-T Cell Therapy (La Nouvelle Orleans Ballroom AB (Ernest N. Morial Convention Center)) -  Nov 4, 2022 - Abstract #ASH2022ASH_1664;    
    These clusters could guide decision-making regarding hospitalization after CAR-T infusion and to preempt early inflammation and disease relapse in high-risk subgroups. Finally, to improve accessibility to cluster assignment, we developed a prediction model for cluster type based on readily available pre-lymphodepletion data and applied it towards an external center cohort as a proof-of-principle.
  • ||||||||||  Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
    A 7-Gene Signature in Unmanipulated Leukaphereses Correlates with in-Vivo CAR T-Cell Expansion and Survival of Lymphoma Patients Receiving Tisagenlecleucel or Axicabtagene Ciloleucel Therapy (La Nouvelle Orleans Ballroom AB (Ernest N. Morial Convention Center)) -  Nov 4, 2022 - Abstract #ASH2022ASH_1661;    
    Our study highlights that unmanipulated leukapheresis share peculiar immunophenotypic and transcriptional features that correlate with CAR T-cell expansion and survival of pts treated with Tisa-cel and Axi-cel. Despite these results warrant functional validation and confirmation in larger cohort (ongoing), the gene signature identified may represent a pre-manufacturing predictive biomarker of CAR T-cell efficacy that might preferentially drive their employment versus other newly approved therapies, such as bispecific T-cell engagers, at the single patient level.
  • ||||||||||  Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
    Functional Disruption of TET2-Mediated Cytosine Oxidation in CAR-T Cells Using IDH1 Neomorph (La Nouvelle Orleans Ballroom C (Ernest N. Morial Convention Center)) -  Nov 4, 2022 - Abstract #ASH2022ASH_1654;    
    This study therefore suggests that the functional disruption of TET2 via the overexpression of the IDH1 neomorph results in augmented memory function of CAR T cells with preservation of effector function. Our discovery introduced an alternative approach for functional TET2 disruption for CAR T cell improvement.
  • ||||||||||  Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
    Double Hit/Double Expressor Lymphomas: A Multicenter Analysis of Survival Outcomes with CD19-Directed CAR T-Cell Therapy (New Orleans Theater C (Ernest N. Morial Convention Center)) -  Nov 4, 2022 - Abstract #ASH2022ASH_1536;    
    This represents a major therapeutic advance for this high-risk population with historically poor survival when treated with chemotherapy and supports early use of CART for these pts in the relapsed setting. DHL pts progressing post-CART have a dismal mOS of 2.7 mon, reflecting the urgent need for effective therapies post-CART failure.
  • ||||||||||  Journal:  New and emerging therapies for the treatment of relapsed/refractory diffuse large B-cell lymphoma. (Pubmed Central) -  Nov 2, 2022   
    These agents include polatuzumab vedotin, tafasitamab, loncastuximab tesirine, selinexor, and anti-CD19 chimeric antigen receptor T-cell therapies such as axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel. This review summarizes the pharmacology, efficacy, safety, dosing, and administration of new agents recently approved for the treatment of relapsed/refractory DLBCL.
  • ||||||||||  Kymriah (tisagenlecleucel-T) / Novartis
    Trial completion date, Trial primary completion date:  BELINDA: Tisagenlecleucel in Adult Patients With Aggressive B-cell Non-Hodgkin Lymphoma (clinicaltrials.gov) -  Nov 2, 2022   
    P3,  N=331, Active, not recruiting, 
    This review summarizes the pharmacology, efficacy, safety, dosing, and administration of new agents recently approved for the treatment of relapsed/refractory DLBCL. Trial completion date: Aug 2028 --> Feb 2026 | Trial primary completion date: Aug 2028 --> Feb 2026
  • ||||||||||  Review, Journal:  Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas. (Pubmed Central) -  Oct 28, 2022   
    Off-label therapies inotuzumab ozogamicin, brentuximab vedotin, and venetoclax demonstrate low rates of treatment-related grade ≥3 infections, while the addition of bortezomib to standard chemotherapy in T-cell malignancies seems to decrease the infection risk during induction. Prophylaxis, immune reconstitution, and vaccinations for each targeted agent are discussed, along with comparisons to adult studies.
  • ||||||||||  Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
    Journal:  Emerging frontiers in immuno- and gene therapy for cancer. (Pubmed Central) -  Oct 26, 2022   
    Prophylaxis, immune reconstitution, and vaccinations for each targeted agent are discussed, along with comparisons to adult studies. In this review, we provide a broad overview of the current state of cell and gene therapy-based approaches for cancer treatment - discussing various effector cell types and their sources, recent advances in both CAR and non-CAR genetic modifications, and highlighting a few promising approaches for increasing in vivo efficacy and persistence of therapeutic drug products.
  • ||||||||||  Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
    Journal, CAR T-Cell Therapy, Cytokine release syndrome:  A Model to Estimate Cytokine Release Syndrome and Neurological Event Management Costs Associated With CAR T-Cell Therapy. (Pubmed Central) -  Oct 23, 2022   
    Across the base case and scenario analysis, liso-cel had the lowest weighted average CRS and NE costs per treated patient compared with axi-cel and tisa-cel owing to lower incidence rates and symptom severity. These findings highlight the economic implications of differences in safety among CAR T-cell therapies.