Open-Label Pilot Study of Genetically Engineered NY-ESO-1 Specific T Cells (GSK3377794) Alone or in Combination with Pembrolizumab in Relapsed and Refractory Multiple Myeloma

NY-ESO-1 TCR T (GSK3377794) are autologous polyclonal T cells transduced by a self-inactivating lentiviral vector to express an affinity-enhanced TCR recognizing NY-ESO-1 or LAGE-1a antigenic peptides in complex with HLA-A2. NY-ESO-1 and LAGE-1a are immunogenic cancer/testis antigens overexpressed in mutiple myeloma (MM) and linked to poor clinical outcome. Patients (pts) with MM who received GSK3377794 after autologous stem cell transplant (ASCT) showed encouraging clinical activity. PD-1 expression on CD8 T cells can occur in GSK3377794-treated MM pts and may limit adaptive immune response; this is a mechanism of resistance/relapse in CD19 CAR T-cell trials.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 406 Source Type: research

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Bargou Andreas Rosenwald Thorsten Stühmer Ellen Leich Approximately 20% of multiple myeloma (MM) cases harbor a point mutation in KRAS. However, there is still no final consent on whether KRAS-mutations are associated with disease outcome. Specifically, no data exist on whether KRAS-mutations have an impact on survival of MM patients at diagnosis in the era of novel agents. Direct blockade of KRAS for therapeutic purposes is mostly impossible, but recently a mutation-specific covalent inhibitor targeting KRASp.G12C entered into clinical trials. However, other KRAS hotspot-mutations exist in MM patients, incl...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
RARITAN, NJ, February 10, 2020 – The Janssen Pharmaceutical Companies of Johnson &Johnson announced today the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) seeking approval of DARZALEX® (daratumumab) in combination with Kyprolis® (carfilzomib) and dexamethasone (DKd) for relapsed/refractory multiple myeloma. The sBLA is supported by results from the Phase 3 CANDOR study, which compared treatment with DKd to carfilzomib and dexamethasone (Kd) in patients with multiple myeloma who relapsed after one to three prior lines of therapy. “Wh...
Source: Johnson and Johnson - Category: Pharmaceuticals Tags: Innovation Source Type: news
AbstractTransfusion-related acute lung injury (TRALI), defined as the onset of acute respiratory distress after blood transfusion, is a rare complication which is a leading cause of transfusion related-mortality. In this retrospective study, we report the French nationwide experience of intravenous immunoglobulin (IVIG)-related TRALI, with a literature review and analysis of management and outcome of this rare condition. With the pharmacovigilance services, we conducted a retrospective multicenter study in the French network of intensive care units with TRALI concomitant to IVIG use and pooled with data from a literature r...
Source: Clinical Rheumatology - Category: Rheumatology Source Type: research
Advent of novel anti-myeloma agents and broader use of stem cell transplant has led to significant improvement in survival of patients (pts) with Multiple Myeloma (MM). However, there are well-described issues with affordability of novel drugs and rapidly escalating price of these agents (Shih et al. JCO 2017), leading to significant disparity among different sociodemographic groups. Hereby, we interrogated the National Cancer Database (NCDB) (which covers 70% of MM patient diagnosed nationwide) to assess impact of insurance type on survival.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 60 Source Type: research
Allogeneic hematopoietic stem cell transplantation (HCT), defined by its underlying graft-versus-multiple myeloma (MM) effect, is a potentially curative approach for high-risk pts. However, relapse remains the main cause of treatment failure. Predictors for post-relapse survival after HCT are not well characterized, and we hypothesized that the time to relapse and the patterns of relapse are prognostic for post-relapse survival.Methods: All pts with MM who underwent a CD34+-selected alloHCT at Memorial Sloan Kettering Cancer Center on protocol (NCT 01131169/01119066) or off study from 01/2010 to 12/2017 and progressed afte...
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 25 Source Type: research
Multiple myeloma (MM) remains incurable with only a small proportion of patients (pts) surviving over 10 years (long-term survivors). It has been over 3 decades since the first autologous stem cell transplantation (ASCT) was done for MM at the University of Texas MD Anderson Cancer Center (MDACC). We sought from this study to describe patient and disease characteristics of long-term MM survivors after ASCT.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 356 Source Type: research
Multiple myeloma (MM) represents 1.8% of all new cancer cases in the U.S. While not curable, advances in treatment, including autologous stem cell transplant (ASCT) and maintenance therapy, have dramatically improved progression free survival (PFS) and overall survival (OS). The Ohio State University began utilizing ASCT for newly diagnosed MM (NDMM) patients in 1992. With the introduction of new, more effective drugs used before and after ASCT over time, we performed retrospective survival analysis in NDMM patients receiving ASCT from 1992-2016.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 336 Source Type: research
In this study, we investigated the link between AF and senescence markers through the assessment of protein expression in the tissue lysates of human appendages from patients in AF, including paroxysmal (PAF) or permanent AF (PmAF), and in sinus rhythm (SR). The major findings of the study indicated that the progression of AF is strongly related to the human atrial senescence burden as determined by p53 and p16 expression. The stepwise increase of senescence (p53, p16), prothrombotic (TF), and proremodeling (MMP-9) markers observed in the right atrial appendages of patients in SR, PAF, and PmAF points toward multiple inter...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Chimeric antigen receptor (CAR) T cell immunotherapy has been a major advancement in cancer therapeutics. Reprogramming of T cells is achieved by using gammaretroviral or lentiviral vectors, which may interfere with human immunodeficiency virus type 1 (HIV-1) nucleic acid amplification testing (NAAT). Here, we describe three clinical scenarios in which CAR T cell immunotherapy interfered with HIV-1 testing, including (i) routine infectious disease screening prior to stem cell transplantation in a 16-year-old female with B cell acute lymphoblastic leukemia, post CAR T cell treatment; (ii) routine infectious disease screenin...
Source: Journal of Clinical Microbiology - Category: Microbiology Authors: Tags: Virology Source Type: research
Miki Kagawa Abe We retrospectively analyzed multiple myeloma (MM) patients who underwent autologous stem cell transplantation (ASCT) without maintenance therapy to assess the impact of recovery of normal immunoglobulin (Ig) on clinical outcomes. The recovery of polyclonal Ig was defined as normalization of all values of serum IgG, IgA, and IgM 1 year after ASCT. Among 50 patients, 26 patients showed polyclonal Ig recovery; 14 patients were in ≥complete response (CR) and 12 remained in non-CR after ASCT. The patients with Ig recovery exhibited a significantly better progression-free survival (PFS, median, ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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