☆ 4.4 Review

Identification and Targeting of Mutant Neoantigens in Multiple Myeloma Treatment

CURRENT ONCOLOGY (2023)

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Article Hematology

Phase 1 study of CART-ddBCMA for the treatment of subjects with relapsed and refractory multiple myeloma

Matthew J. Frigault et al.

Summary: This study evaluated the safety and efficacy of a novel B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T construct, CART-ddBCMA, in patients with relapsed and refractory multiple myeloma (RRMM). The results showed that CART-ddBCMA was well tolerated, with manageable side effects, and demonstrated durable responses in RRMM patients.

BLOOD ADVANCES (2023)

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Article Oncology

Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy

Alfred L. Garfall et al.

Summary: This study conducted a clinical trial of CAR T cells in multiple myeloma patients and found that it can be a safe and effective treatment for the disease. The results demonstrate the relationship between early treatment and CAR T cell reexpansion and durable clinical response.

BLOOD CANCER DISCOVERY (2023)

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Review Biochemistry & Molecular Biology

Neoantigens: promising targets for cancer therapy

Na Xie et al.

Summary: Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies, providing emerging targets for personalized cancer immunotherapies and potential predictors for tumor survival prognosis and immune checkpoint blockade responses.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2023)

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Review Hematology

Chimeric antigen receptor T-cells, bispecific antibodies, and antibody-drug conjugates for multiple myeloma: An update

Arjun Lakshman et al.

Summary: For multiple myeloma patients refractory to current therapies, CAR T-lymphocytes, bsAbs, and ADCs show potential with ide cel and belamaf approved in the relapsed/refractory setting. bsAbs demonstrate promising quick and deep responses in clinical trials.

AMERICAN JOURNAL OF HEMATOLOGY (2022)

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Article Oncology

High efficacy and safety of CD38 and BCMA bispecific CAR-T in relapsed or refractory multiple myeloma

Yuanyan Tang et al.

Summary: The study showed that BCMA-CD38 bispecific CAR-T cell therapy is effective in treating R/R MM patients, with high response rate, low recurrence rate, and manageable cytokine release syndrome (CRS), providing a promising treatment option.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2022)

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Article Oncology

A combination of humanized anti-BCMA and murine anti-CD38 CAR-T cell therapy in patients with relapsed or refractory multiple myeloma

Huan Zhang et al.

Summary: This study evaluated the safety and efficacy of a combination of humanized anti-BCMA and murine anti-CD38 CAR-T cell therapy in patients with relapsed or refractory multiple myeloma. The results showed that the combination therapy has the potential to significantly improve overall response rate and survival rate in R/RMM patients, but may also lead to adverse reactions in some patients.

LEUKEMIA & LYMPHOMA (2022)

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Article Hematology

CAR-T cell therapy targeting B cell maturation antigen is effective for relapsed/refractory multiple myeloma, including cases with poor performance status

Juan Du et al.

Summary: This study evaluated the efficacy of BCMA CAR-T cell therapy in relapsed/refractory multiple myeloma patients, showing that HDS269B therapy is safe and effective for these patients, including those with ECOG 3-4 grades.

AMERICAN JOURNAL OF HEMATOLOGY (2022)

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Article Immunology

Correlation of Cytokine Release Syndrome With Prognosis After Chimeric Antigen Receptor T Cell Therapy: Analysis of 54 Patients With Relapsed or Refractory Multiple Myeloma

Xue Wang et al.

Summary: This study confirmed the effectiveness of chimeric antigen receptor T (CAR-T) cell therapy in treating multiple myeloma. However, the severity of cytokine release syndrome (CRS) can impact patient survival. Analysis of 54 patients revealed a correlation between CRS severity and progression-free survival (PFS) and overall survival (OS), as well as an independent association between bone marrow tumor burden and CRS.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Medicine, General & Internal

Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody

Ajai Chari et al.

Summary: Talquetamab treatment exhibited common adverse events like cytokine release syndrome, skin-related events, and dysgeusia, which were primarily low-grade; however, the drug induced substantial response among patients with heavily pretreated relapsed or refractory multiple myeloma.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Article Education, Scientific Disciplines

Antibodies and bispecifics for multiple myeloma: effective effector therapy

Christopher Cipkar et al.

Summary: The therapeutic landscape for multiple myeloma has drastically changed in the past two decades, with the introduction of novel immunotherapies that have improved treatment responses, remissions, and overall survival. Various antibodies, such as daratumumab and belantamab mafodotin, are being used to specifically target malignant plasma cells, while bispecific T-cell antibodies are being developed to engage the immune system. These advancements have significantly impacted front-line and relapse settings for the treatment of multiple myeloma.

HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM (2022)

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Review Immunology

Manipulating T-cell metabolism to enhance immunotherapy in solid tumor

Chen Chen et al.

Summary: Cellular metabolism plays a critical role in tumor cells and T cells. Dysregulated metabolism is a hallmark of cancer and impacts the function of T cells. The interaction between tumor and T cell metabolism can affect T cell responses. Metabolic competition in the tumor ecosystem suppresses effector T cells. Targeting metabolic reprogramming shows promise in cancer treatment.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Medicine, General & Internal

Teclistamab in Relapsed or Refractory Multiple Myeloma

Philippe Moreau et al.

Summary: Teclistamab demonstrated promising efficacy in patients with relapsed or refractory multiple myeloma, leading to high rates of deep and durable response. Common adverse events included cytokine release syndrome, cytopenias, and infections, with toxic effects mostly grade 1 or 2.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Article Oncology

γ-secretase inhibitors augment efficacy of BCMA-targeting bispecific antibodies against multiple myeloma cells without impairing T-cell activation and differentiation

Hailin Chen et al.

Summary: This study defined the effects of gamma-secretase inhibitors (GSIs) on multiple myeloma and demonstrated their potential to enhance immune response and improve patient outcomes when combined with BCMA-targeting immunotherapies. The results showed that GSIs increased membrane BCMA densities and enhanced T-cell-mediated MM cell lysis. In addition, GSIs cleared soluble BCMA from circulation and improved the efficacy of BCMA-targeting treatment in mice models.

BLOOD CANCER JOURNAL (2022)

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Article Medicine, Research & Experimental

NAIRscore as a biomarker for the quality of immune response to neoantigens is related with an increased overall survival in multiple myeloma

Xingxing Jian et al.

Summary: Neoantigen provides a promising breakthrough in tumor immunotherapy, and this study developed a pipeline to predict neoantigens based on somatic mutations and gene-expression profiles. The study also constructed a neoantigen immune response score (NAIRscore) integrating neoantigen load, cytolytic score, and HLA-I score, which showed competitive advantage in stratifying multiple myeloma samples and predicting overall survival.

MOLECULAR THERAPY-NUCLEIC ACIDS (2022)

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Article Immunology

Prolonged hematological toxicity in patients receiving BCMA/CD19 CAR-T-cell therapy for relapsed or refractory multiple myeloma

Hujun Li et al.

Summary: Severe hematological toxicity (HT) remains a challenge in CAR-T cell therapy for relapsed or refractory multiple myeloma (R/R MM). This study found that the incidence of severe cytopenia was high after combined infusion of anti-CD19 and anti-BCMA CAR-T cells, and prolonged HT was associated with poor outcomes in MM patients.

FRONTIERS IN IMMUNOLOGY (2022)

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Review Oncology

CAR T-Cell Therapy for Patients with Multiple Myeloma: Current Evidence and Challenges

Matthew J. Rendo et al.

Summary: CAR T-cell therapies show potential in the treatment of multiple myeloma, but still face challenges.

BLOOD AND LYMPHATIC CANCER-TARGETS AND THERAPY (2022)

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Article Oncology

Cancer Statistics, 2021

Rebecca L. Siegel et al.

Summary: Every year, the American Cancer Society projects the numbers of new cancer cases and deaths in the United States, with the latest data showing a significant decline in lung cancer mortality, while prostate cancer mortality has plateaued and breast and colorectal cancer mortality have slowed. Improvements in treatment have accelerated progress against lung cancer, leading to a record drop in overall cancer mortality.

CA-A CANCER JOURNAL FOR CLINICIANS (2021)

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Article Biochemistry & Molecular Biology

Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma

Zhuting Hu et al.

Summary: Personal neoantigen peptide vaccines induce long-lasting T cell responses in melanoma patients, broadening the spectrum of tumor-specific cytotoxicity and resulting in diverse T cell clones with cytotoxic gene signatures.

NATURE MEDICINE (2021)

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Article Oncology

A bispecific CAR-T cell therapy targeting BCMA and CD38 in relapsed or refractory multiple myeloma

Heng Mei et al.

Summary: Bispecific BM38 CAR-T cells showed strong efficacy in patients with refractory or relapsed multiple myeloma (RRMM), with good clinical responses and manageable toxicities.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2021)

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Review Immunology

Neoantigen: A New Breakthrough in Tumor Immunotherapy

Zheying Zhang et al.

Summary: Cancer immunotherapy enhances the body's immune response to target and eliminate cancer cells, with a focus on the emerging approach of tumor neoantigens. Studies have shown the relationship between neoantigens and T cell recognition of cancer cells, highlighting the potential of vaccines developed against these specific antigens in clinical trials.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Hematology

Preclinical activity and determinants of response of the GPRC5DxCD3 bispecific antibody talquetamab in multiple myeloma

Christie P. M. Verkleij et al.

Summary: GPRC5D-targeting T-cell redirecting bispecific antibody talquetamab demonstrates potent anti-myeloma activity, effectively killing MM cells with high GPRC5D expression levels, especially with high effector:target ratio. Combination therapy with daratumumab or pomalidomide enhances talquetamab-mediated lysis of primary MM cells in an additive fashion.

BLOOD ADVANCES (2021)

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Article Medicine, General & Internal

Teclistamab, a B-cell maturation antigenxCD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study

Saad Z. Usmani et al.

Summary: The study evaluated the safety, tolerability, and efficacy of the novel therapy teclistamab for relapsed or refractory multiple myeloma. The results showed promising response rates and durable efficacy in patients treated at the recommended phase 2 dose, with good overall safety profiles.

LANCET (2021)

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Article Medicine, General & Internal

Immune checkpoint inhibitors in melanoma

Matteo S Carlino et al.

LANCET (2021)

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Article Biochemistry & Molecular Biology

Intron retention-induced neoantigen load correlates with unfavorable prognosis in multiple myeloma

Chuanpeng Dong et al.

Summary: The study identified high IR-neoAg load as a predictor of poor overall survival in both newly diagnosed and relapsed multiple myeloma (MM) patients. Furthermore, the poor clinical outcome in MM patients with high IR-neoAg load was associated with high expression levels of T-cell co-inhibitory molecules and elevated interferon signaling activity.

ONCOGENE (2021)

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Article Hematology

Indatuximab ravtansine plus dexamethasone with lenalidomide or pomalidomide in relapsed or refractory multiple myeloma: a multicentre, phase 1/2a study

Kevin R. Kelly et al.

Summary: The study aimed to evaluate the safety and activity of indatuximab ravtansine in combination with immunomodulatory drugs in patients with relapsed or refractory multiple myeloma. The results showed that this combination therapy demonstrated good tolerability and antitumor activity in the patient population.

LANCET HAEMATOLOGY (2021)

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Article Oncology

Targeting public neoantigens for cancer immunotherapy

Alexander H. Pearlman et al.

Summary: Immunotherapy can target public neoantigens for cancer treatment, which focuses on proteins crucial for tumor growth and can be applied to a broad range of patients. However, identifying suitable public neoantigen targets and developing corresponding therapeutic agents still pose challenges.

NATURE CANCER (2021)

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Article Biochemistry & Molecular Biology

Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer

Zhenyu Ding et al.

Summary: Neoantigen vaccine therapy provides new evidence and therapeutic opportunities for lung cancer treatment, with an objective effectiveness rate of 25% and a disease control rate of 75%, showing promising results despite overall unsatisfactory efficacy.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Article Oncology

Mutation-derived Neoantigen-specific T-cell Responses in Multiple Myeloma

Deepak Perumal et al.

CLINICAL CANCER RESEARCH (2020)

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Article Oncology

Anti-B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma

Max S. Topp et al.

JOURNAL OF CLINICAL ONCOLOGY (2020)

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Article Hematology

The critical role of CD4+ T cells in PD-1 blockade against MHC-II-expressing tumors such as classic Hodgkin lymphoma

Joji Nagasaki et al.

BLOOD ADVANCES (2020)

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Article Education, Scientific Disciplines

Bispecifics, trispecifics, and other novel immune treatments in myeloma

Guido Lancman et al.

HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM (2020)

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Systematically Characterizing A-to-I RNA Editing Neoantigens in Cancer

Chi Zhou et al.

FRONTIERS IN ONCOLOGY (2020)

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Review Hematology

Frontline therapy for newly diagnosed patients with multiple myeloma

Sung-Hoon Jung et al.

BLOOD RESEARCH (2020)

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Trispecific antibodies enhance the therapeutic efficacy of tumor-directed T cells through T cell receptor co-stimulation

Lan Wu et al.

NATURE CANCER (2020)

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A Phase I Study to Assess the Safety and Pharmacokinetics of Single-agent Lorvotuzumab Mertansine (IMGN901) in Patients with Relapsed and/or Refractory CD-56-positive Multiple Myeloma

Sikander Ailawadhi et al.

CLINICAL LYMPHOMA MYELOMA & LEUKEMIA (2019)

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Indatuximab Ravtansine (BT062) Monotherapy in Patients With Relapsed and/or Refractory Multiple Myeloma

Sundar Jagannath et al.

CLINICAL LYMPHOMA MYELOMA & LEUKEMIA (2019)

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Antibody-drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study

Suzanne Trudel et al.

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Monoclonal gammopathy of undetermined significance

Tarek H. Mouhieddine et al.

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B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma

Adam D. Cohen et al.

JOURNAL OF CLINICAL INVESTIGATION (2019)

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Pediatric patients with acute lymphoblastic leukemia generate abundant and functional neoantigen-specific CD8+ T cell responses

Anthony E. Zamora et al.

SCIENCE TRANSLATIONAL MEDICINE (2019)

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Determinants for Neoantigen Identification

Andrea Garcia-Garijo et al.

FRONTIERS IN IMMUNOLOGY (2019)

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A combination of humanised anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, phase 2 trial

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LANCET HAEMATOLOGY (2019)

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Diego Ellerman

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Bortezomib retreatment for relapsed and refractory multiple myeloma in real-world clinical practice

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HEALTH SCIENCE REPORTS (2019)

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The Role of B-Cell Maturation Antigen in the Biology and Management of, and as a Potential Therapeutic Target in, Multiple Myeloma

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Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma

Brian A. Walker et al.

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Improvement in Overall Survival With Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

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JOURNAL OF CLINICAL ONCOLOGY (2018)

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Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers

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High somatic mutation and neoantigen burden are correlated with decreased progression-free survival in multiple myeloma

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