Cancers, Vol. 11, Pages 2009: Immunotherapy for Multiple Myeloma

Cancers, Vol. 11, Pages 2009: Immunotherapy for Multiple Myeloma Cancers doi: 10.3390/cancers11122009 Authors: Tamura Ishibashi Sunakawa Inokuchi Despite therapeutic advances over the past decades, multiple myeloma (MM) remains a largely incurable disease with poor prognosis in high-risk patients, and thus new treatment strategies are needed to achieve treatment breakthroughs. MM represents various forms of impaired immune surveillance characterized by not only disrupted antibody production but also immune dysfunction of T, natural killer cells, and dendritic cells, although immunotherapeutic interventions such as allogeneic stem-cell transplantation and dendritic cell-based tumor vaccines were reported to prolong survival in limited populations of MM patients. Recently, epoch-making immunotherapies, i.e., immunomodulatory drug-intensified monoclonal antibodies, such as daratumumab combined with lenalidomide and chimeric antigen receptor T-cell therapy targeting B-cell maturation antigen, have been developed, and was shown to improve prognosis even in advanced-stage MM patients. Clinical trials using other antibody-based treatments, such as antibody drug-conjugate and bispecific antigen-directed CD3 T-cell engager targeting, are ongoing. The manipulation of anergic T-cells by checkpoint inhibitors, including an anti-T-cell immunoglobulin and ITIM domains (TIGIT) antibody, also has the potential to prolong survival times. Those new treatments or their combina...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research

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Publication date: Available online 25 January 2020Source: Best Practice &Research Clinical HaematologyAuthor(s): Chutima Kunacheewa, Elisabet E. ManasanchAbstractMultiple myeloma, a bone marrow cancer, is preceded by precursor stages called monoclonal gammopathy of unknown significance and smoldering multiple myeloma. Over the past few years, highly effective and safe therapies have been made available to treat multiple myeloma. This represents a major breakthrough and has major therapeutic implications. Treatment for multiple myeloma has evolved to include treatment of precursor stages (early treatment) as these thera...
Source: Best Practice and Research Clinical Haematology - Category: Hematology Source Type: research
High dose chemotherapy followed by hematopoietic cell transplantation (HCT) is an intensive cancer treatment associated with devastating complications. Persistent physical inactivity after HCT is sufficient to cause muscle mass loss, decreased strength, physical deconditioning, and potential progression to disability. Sustainable physical activity incorporated into activities of daily living may break this negative cycle. This pilot, randomized controlled trial tested the feasibility and preliminary effects of a free-living physical activity intervention (STEPS) compared to usual care on fatigue (primary outcome), function...
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 110 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
Cellular immunotherapy is a rapidly progressing field in multiple myeloma (MM). Multiple clinical trials have reported impressive efficacy of B cell maturation antigen (BCMA) directed chimeric antigen receptor cell therapy (BCMA CART) in MM. While trials demonstrated a high response rate, the durable response rate is around 30%. Most patients lose their CART cells, and the disease relapses within the first year, suggesting an inhibition by the MM tumor microenvironment (TME). Therefore strategies to overcome this inhibition would represent a major advance in this field.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 333 Source Type: research
BMT CTN 1401 is an academically led randomized study of a personalized cancer vaccine in which the combination of DC/MM fusion vaccine and lenalidomide maintenance after autoHCT is compared with maintenance alone as upfront treatment of MM (NCT#02728102). Assessment of the percentage of patients achieving CR and therapy-induced changes in MM-specific immunity are the primary clinical and immunologic endpoints, respectively. The protocol represents a transformative open source approach to cell therapy in MM and required collection of tumor cells prior to treatment initiation and vaccine production at day 60 after autoHCT.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 83 Source Type: research
Killer Immunoglobulin-like Receptor (KIR) inhibition is known to influence the cytotoxic effects of natural killer (NK) cells against cancer cells. KIRs can be protective against relapse in myeloma (MM) (Gabriel et al Blood 2010, Kr öger et al leukemia 2011) by NK cell licencing or through blocking of the inhibitory KIR receptors such as NKG2A (Mahaweni et al, 2018).
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 483 Source Type: research
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 resista...
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 406 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
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