☆ 3.8 Review

Cellular Immunotherapies for Multiple Myeloma: Current Status, Challenges, and Future Directions

ONCOLOGY AND THERAPY (2022)

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Article Hematology

HLA informs risk predictions after haploidentical stem cell transplantation with posttransplantation cyclophosphamide

Ephraim J. Fuchs et al.

Summary: HLA factors play an important role in the success of haploidentical transplantation. Disease-free survival is associated with matching status at individual HLA loci, with HLA-DRB1 and -DPB1 mismatches and HLA-C,-B leader, and -DQB1 matching being favorable. Considering HLA factors may help optimize the selection of haploidentical related donors.

BLOOD (2022)

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Article Hematology

Carfilzomib and dexamethasone maintenance following salvage ASCT in multiple myeloma: A randomised phase 2 trial by the Nordic Myeloma Study Group

Henrik Gregersen et al.

Summary: The study demonstrated that maintenance therapy with carfilzomib and dexamethasone after salvage ASCT can prolong time to progression (TTP) by approximately 8 months, with generally manageable toxicity and well-tolerated adverse effects such as thrombocytopenia, anemia, hypertension, dyspnea, and bacterial infections.

EUROPEAN JOURNAL OF HAEMATOLOGY (2022)

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Review Hematology

Defining the undetectable: The current landscape of minimal residual disease assessment in multiple myeloma and goals for future clarity

Benjamin T. Diamond et al.

Summary: Multiple myeloma lacks a established curative therapy, but modern four-drug regimens can achieve a nearly 100% overall response rate. Efforts are focused on measuring minimal residual disease (MRD) for prognostic metrics and therapeutic response evaluation, using methods such as flow cytometry and next generation sequencing. New technologies are being developed for MRD assessment in multiple myeloma.

BLOOD REVIEWS (2021)

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Article Biophysics

Upfront stem cell transplantation for newly diagnosed multiple myeloma with del(17p) and t(4;14): a study from the CMWP-EBMT

Nico Gagelmann et al.

Summary: The study found that for patients with t(4;14), tandem autologous and tandem autologous/reduced-intensity allogeneic transplantation were associated with better progression-free survival (PFS), while for patients with del(17p), there was no significant difference in outcome.

BONE MARROW TRANSPLANTATION (2021)

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Review Biophysics

Chimeric antigen receptor T cell therapy in multiple myeloma: promise and challenges

Binod Dhakal et al.

Summary: CAR-T cell therapy has shown unprecedented efficacy in treating multiple myeloma, but still faces challenges such as relapse, drug resistance, and toxic reactions. The development of multi-targeted CAR-T antigens and combinatorial therapies is the direction to overcome these challenges.

BONE MARROW TRANSPLANTATION (2021)

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Article Hematology

Early relapse after high-dose melphalan autologous stem cell transplant predicts inferior survival and is associated with high disease burden and genetically high-risk disease in multiple myeloma

Ceri Bygrave et al.

Summary: Despite equal access to subsequent therapies, myeloma patients who relapse early within 12 months of autologous stem cell transplant have significantly worse progression-free survival and overall survival compared to later relapsing patients, highlighting the urgent need for improved outcome prediction and early intervention strategies.

BRITISH JOURNAL OF HAEMATOLOGY (2021)

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Letter Hematology

Bi38-3 is a novel CD38/CD3 bispecific T-cell engager with low toxicity for the treatment of multiple myeloma

Maxime Fayon et al.

HAEMATOLOGICA (2021)

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Article Oncology

Salvage autologous transplant and lenalidomide maintenance vs. lenalidomide/dexamethasone for relapsed multiple myeloma: the randomized GMMG phase III trial ReLApsE

Hartmut Goldschmidt et al.

Summary: The efficacy of salvage high-dose chemotherapy and autologous stem cell transplantation (sHDCT/ASCT) for relapsed and/or refractory multiple myeloma (RRMM) has not been clearly defined in the era of continuous novel agent treatment, however, patients who received this treatment may have benefited.

LEUKEMIA (2021)

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Article Oncology

Bortezomib-based induction, high-dose melphalan and lenalidomide maintenance in myeloma up to 70 years of age

Elias K. Mai et al.

Summary: Intensive upfront therapy for newly-diagnosed multiple myeloma patients up to age 70 is feasible, with similar treatment adherence across age groups but increased overall toxicity in older patients. Age does not impact progression-free or overall survival outcomes in this setting.

LEUKEMIA (2021)

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Article Biotechnology & Applied Microbiology

Development of CAR T Cells Expressing a Suicide Gene Plus a Chimeric Antigen Receptor Targeting Signaling Lymphocytic-Activation Molecule F7

Christina Amatya et al.

Summary: CARs targeting SLAMF7 show promise for MM therapy due to specific expression on MM cells, and CD28-containing CARs exhibit superior anti-tumor activity compared to 4-1BB-containing CARs. Inclusion of a suicide gene in SLAMF7-targeting CAR T cells is prudent to eliminate cells expressing SLAMF7 on normal leukocytes when necessary.

MOLECULAR THERAPY (2021)

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Article Hematology

A phase 1 study of a novel fully human BCMA-targeting CAR (CT103A) in patients with relapsed/refractory multiple myeloma

Di Wang et al.

Summary: CT103A, a fully human BCMA-specific CAR T-cell therapy, has shown safety and high efficacy in patients with relapsed/refractory multiple myeloma, including those who had prior exposures to murine BCMA CAR therapy. Its overall response rate reaches 100%, with a significant portion achieving complete response or stringent complete response. Hematologic toxicities are common adverse events, but no immune effector cell-associated neurotoxicity syndrome was observed. Detection of CAR transgenes and median CAR transgene persistence support the potential of CT103A as a promising therapy for RRMM.

BLOOD (2021)

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Article Biophysics

Evaluation of EuroFlow minimal residual disease measurement and donor chimerism monitoring following tandem auto-allogeneic transplantation for multiple myeloma

Joanne L. C. Tan et al.

Summary: The presence of MRD post-alloHSCT is associated with inferior prognosis, while attainment or maintenance of MRD negativity predicts reduced relapse risk. Full CD3(+) donor chimerism is linked to an increased risk of acute GVHD, but does not impact PFS or OS.

BONE MARROW TRANSPLANTATION (2021)

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Article Biophysics

Tandem autologous hematopoietic cell transplantation with sequential use of total marrow irradiation and high-dose melphalan in multiple myeloma

Sebastian Giebel et al.

Summary: The study aimed to evaluate the safety and efficacy of tandem autologous hematopoietic cell transplantation in patients with multiple myeloma. The results showed that the conditioning with TMI in sequence with high-dose melphalan had very good toxicity profile with encouraging early efficacy, with overall and progression-free survival probabilities at 5 years being 74% and 55%, respectively.

BONE MARROW TRANSPLANTATION (2021)

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Meeting Abstract Hematology

Addition of Isatuximab to Lenalidomide, Bortezomib and Dexamethasone As Induction Therapy for Newly-Diagnosed, Transplant-Eligible Multiple Myeloma Patients: The Phase III GMMG-HD7 Trial

Hartmut Goldschmidt et al.

BLOOD (2021)

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Article Oncology

Preclinical development of CD126 CAR-T cells with broad antitumor activity

Ameet K. Mishra et al.

Summary: CD126 is expressed by various tumors and CAR-T cells targeting CD126 show efficient killing of tumor cells. Binding of soluble interleukin-6 receptor (sIL-6R) by CAR-T cells can mitigate cytokine release syndrome. CD126 provides a novel therapeutic target for CAR-T cells for many tumors with low toxicity risk.

BLOOD CANCER JOURNAL (2021)

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Article Oncology

Lenalidomide versus bortezomib maintenance after frontline autologous stem cell transplantation for multiple myeloma

Marc-Andrea Baertsch et al.

Summary: In patients with multiple myeloma post autologous stem cell transplantation, maintenance treatment with bortezomib and lenalidomide showed no significant difference in progression-free survival and overall survival.

BLOOD CANCER JOURNAL (2021)

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Article Medicine, General & Internal

Carfilzomib, lenalidomide, dexamethasone, and cyclophosphamide (KRdc) as induction therapy for transplant-eligible, newly diagnosed multiple myeloma patients (Myeloma XI plus ): Interim analysis of an open-label randomised controlled trial

Graham H. Jackson et al.

Summary: The study evaluated the efficacy and safety of using Carfilzomib in combination with other drugs to treat newly diagnosed multiple myeloma patients. Patients receiving Carfilzomib combination therapy were more likely to achieve better partial response and had significantly longer progression-free survival compared to the control group.

PLOS MEDICINE (2021)

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Article Oncology

Sequential CD19 and BCMA-specific CAR T-cell treatment elicits sustained remission of relapsed and/or refractory myeloma

Lingzhi Yan et al.

Summary: This study demonstrates the safety and efficacy of sequential infusion of CD19-CART and BCMA-CART for RRMM, with a significant overall response rate and promising results in some patients.

CANCER MEDICINE (2021)

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Article Oncology

Blockade of AIM2 inflammasome or α1-AR ameliorates IL-1β release and macrophage-mediated immunosuppression induced by CAR-T treatment

Dan Liu et al.

Summary: This study demonstrates that CAR-T therapy induces activation of the AIM2 inflammasome in macrophages, leading to the release of bioactive IL-1 beta. Additionally, the alpha 1-AR-mediated adrenergic signaling enhances the priming of AIM2 inflammasome, while tumor cell DNA release triggers inflammasome activation. The interaction between CAR-T cells and tumor cells causes a phenotypic switch in macrophages, inhibiting the cytotoxicity of CAR-T cells and T cell proliferation through upregulation of PD-L1 and IDO.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (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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Article Oncology

Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

M. A. Dimopoulos et al.

ANNALS OF ONCOLOGY (2021)

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Review Hematology

Improving outcomes for patients with relapsed multiple myeloma: Challenges and considerations of current and emerging treatment options

Karthik Ramasamy et al.

Summary: Despite the introduction of new therapies, multiple myeloma remains incurable and the treatment landscape is becoming increasingly complex. Relapsed refractory multiple myeloma presents a significant clinical challenge, with a highly heterogeneous patient population requiring careful consideration for treatment selection. Multiple treatment options are continually growing, with emerging novel therapies under clinical development.

BLOOD REVIEWS (2021)

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Article Oncology

Mortality from Multiple Myeloma Within One Year Following Autologous Stem Cell Transplantation: Defining an Ultra-high Risk Population

Hannah M. Cherniawsky et al.

Summary: Despite improvements in therapy, a small proportion of patients with newly diagnosed multiple myeloma who undergo autologous stem cell transplantation (ASCT) experience early mortality (EM) within 1 year of transplant. Factors such as anemia, hypercalcemia, high-risk cytogenetics, and elevated lactate dehydrogenase are associated with EM post-ASCT. Most patients with EM post-ASCT receive second-line chemotherapy, but survival time is short.

CLINICAL LYMPHOMA MYELOMA & LEUKEMIA (2021)

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Article Oncology

Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial

Thierry Facon et al.

Summary: In patients with newly diagnosed multiple myeloma who are ineligible for stem-cell transplantation, daratumumab plus lenalidomide and dexamethasone significantly improved overall survival and progression-free survival with no new safety concerns.

LANCET ONCOLOGY (2021)

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Article Oncology

Carfilzomib with cyclophosphamide and dexamethasone or lenalidomide and dexamethasone plus autologous transplantation or carfilzomib plus lenalidomide and dexamethasone, followed by maintenance with carfilzomib plus lenalidomide or lenalidomide alone for patients with newly diagnosed multiple myeloma (FORTE): a randomised, open-label, phase 2 trial

Francesca Gay et al.

Summary: This study aimed to evaluate the efficacy and safety of different carfilzomib-based treatment approaches and maintenance therapy, showing that KRd plus ASCT demonstrated superiority in improving responses compared with other treatments, and carfilzomib plus lenalidomide as maintenance therapy improved progression-free survival compared with lenalidomide alone.

LANCET ONCOLOGY (2021)

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Article Oncology

Evaluation of Sustained Minimal Residual Disease Negativity With Daratumumab-Combination Regimens in Relapsed and/or Refractory Multiple Myeloma: Analysis of POLLUX and CASTOR

Herve Avet-Loiseau et al.

Summary: In relapsed and/or refractory multiple myeloma, daratumumab reduced the risk of progression or death by more than 60% in the POLLUX and CASTOR trials. The use of daratumumab-based combinations resulted in higher rates of sustained MRD negativity compared to standard of care, leading to improved clinical outcomes and prolonged progression-free survival.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Article Biochemistry & Molecular Biology

Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma

Matteo C. Da Via et al.

Summary: BCMA serves as a target for immunotherapies and a biomarker for tumor load in MM. The study found a correlation between TNFRSF17 loss and BCMA loss, leading to immune escape. Heterozygous TNFRSF17 deletion at baseline in high hyperhaploid MM patients may increase the risk of BCMA loss after immunotherapy.

NATURE MEDICINE (2021)

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Article Medicine, General & Internal

Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma

Nikhil C. Munshi et al.

Summary: The phase 2 study confirmed the efficacy and safety of ide-cel in patients with relapsed and refractory myeloma, with a majority of patients achieving responses and 26% achieving MRD-negative status. Despite the high response rate, almost all patients experienced grade 3 or 4 toxic effects, including hematologic toxic effects and cytokine release syndrome.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Article Multidisciplinary Sciences

Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with multiple myeloma

Mehmet Kemal Samur et al.

Summary: Relapse following BCMA targeted CAR T-cell therapy in multiple myeloma patients is often due to biallelic loss of BCMA, which hinders the proliferation of CAR T cells and results in lack of response to retreatment. Single cell genomic characterization is essential for detecting BCMA gene alterations to improve treatment outcomes.

NATURE COMMUNICATIONS (2021)

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Article Hematology

Daratumumab plus RVd for newly diagnosed multiple myeloma: final analysis of the safety run-in cohort of GRIFFIN

Peter M. Voorhees et al.

Summary: The phase 2 GRIFFIN study explores the efficacy of D-RVd combination therapy in transplant-eligible newly diagnosed multiple myeloma patients. The study shows promising results in terms of high stringent complete response rate and minimal residual disease negativity at the end of maintenance therapy. The safety profile of the treatment regimen is consistent with previous studies, and with over 3 years of follow-up, D-RVd demonstrates durable responses that deepen with D-R maintenance.

BLOOD ADVANCES (2021)

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Article Hematology

Long-term outcome after allogeneic stem cell transplantation in multiple myeloma

Sini Luoma et al.

Summary: The study explored the role of allogeneic hematopoietic stem cell transplantation in multiple myeloma, showing that this approach can lead to long-term survival in a small subgroup of patients, and auto-allo-SCT may be considered for younger patients.

ANNALS OF HEMATOLOGY (2021)

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Article Hematology

Progression signature underlies clonal evolution and dissemination of multiple myeloma

Yu Jia Shen et al.

Summary: Clonal evolution plays a key role in tumor progression, dissemination, and relapse in multiple myeloma (MM). By developing a clone-tracking system, researchers studied clonal behavior in the bone marrow microenvironment, identifying specific clones able to adapt and colonize distant sites. RNA sequencing revealed a progression signature in MM tumor cells, leading to the prediction of 28 master regulators, with HMGA1 and PA2G4 validated as key players in MM progression and dissemination, impacting cell functions like proliferation, migration, and adhesion. This study successfully replicates key characteristics of human MM disease progression and suggests potential therapeutic targets.

BLOOD (2021)

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Article Biophysics

Second allogeneic transplants for multiple myeloma: a report from the EBMT Chronic Malignancies Working Party

Patrick J. Hayden et al.

Summary: For patients with relapsed multiple myeloma, receiving a second allo-HCT from a HLA-identical sibling donor for both transplants is associated with higher overall survival rates. Additionally, an interval of more than 2 years between transplants is associated with superior 5-year survival rates.

BONE MARROW TRANSPLANTATION (2021)

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Article Hematology

Guidelines on the diagnosis, investigation and initial treatment of myeloma: a British Society for Haematology/UK Myeloma Forum Guideline

Jonathan Sive et al.

BRITISH JOURNAL OF HAEMATOLOGY (2021)

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Article Oncology

Bone Marrow Mesenchymal Stromal Cells Can Render Multiple Myeloma Cells Resistant to Cytotoxic Machinery of CAR T Cells through Inhibition of Apoptosis

Lisa C. Holthof et al.

Summary: The microenvironment of multiple myeloma can impact therapy outcome, with bone marrow mesenchymal stromal cells protecting MM cells from lysis by certain CAR T cells. BMMSCs did not protect against high-affinity, strongly lytic CAR T cells, but significantly protected against lower affinity, moderately lytic CAR T cells in a cell-cell contact-dependent manner. The study suggests that inhibition of antiapoptotic proteins upregulated in MM cells through BMMSC interactions may improve the outcome of CAR T cell or conventional CTL therapies.

CLINICAL CANCER RESEARCH (2021)

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Article Biochemistry & Molecular Biology

CARAMBA: a first-in-human clinical trial with SLAMF7 CAR-T cells prepared by virus-free Sleeping Beauty gene transfer to treat multiple myeloma

Sabrina Prommersberger et al.

Summary: Clinical development of CAR-T-cell therapy has been advanced by synthetic biology, genetic engineering, and clinical-grade manufacturing, with the goal of providing safe, effective, and economically sustainable treatment. The CARAMBA project aims to demonstrate virus-free CAR gene transfer using advanced SB transposon technology, potentially improving vector procurement, CAR-T manufacturing, and distribution. The project focuses on utilizing SB-based CAR-T cells targeting the SLAMF7 antigen in multiple myeloma, with promising preclinical results indicating potent anti-myeloma activity.

GENE THERAPY (2021)

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Review Medicine, General & Internal

Successful Treatment of Relapsed/Refractory Extramedullary Multiple Myeloma With Anti-BCMA CAR-T Cell Therapy Followed by Haploidentical Hematopoietic Stem Cell Transplantation: A Case Report and a Review of the Contemporary Literature

Ying Qian et al.

Summary: Extramedullary multiple myeloma (EMM) is a subtype with poor prognosis, lacking established standard treatments. A case study of a relapsed EMM patient who underwent myeloablative haploidentical hematopoietic stem cell transplantation after CAR-T cell therapy suggests a potential salvage treatment strategy for such cases.

FRONTIERS IN MEDICINE (2021)

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Article Biophysics

Outcomes after delayed and second autologous stem cell transplant in patients with relapsed multiple myeloma

Christopher Lemieux et al.

Summary: This study evaluated the outcomes of patients with relapsed multiple myeloma undergoing delayed or second autologous stem cell transplant. The results showed that transplant in first relapse was associated with superior progression-free survival and overall survival compared to later lines of therapy, and achieving a progression-free survival of >= 36 months with prior therapy was also associated with improved survival.

BONE MARROW TRANSPLANTATION (2021)

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Article Oncology

Outcomes of upfront autologous hematopoietic cell transplantation in patients with multiple myeloma who are 75 years old or older

Pashna N. Munshi et al.

Summary: Autologous hematopoietic stem cell transplantation in multiple myeloma patients aged 75 years and above has shown excellent 2-year outcomes, but remains underutilized in this age group with significant racial and gender disparities.

CANCER (2021)

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Meeting Abstract Oncology

Improved outcomes with maintenance therapy after salvage autologous hematopoietic cell transplantation (AHCT) in multiple myeloma: A CIBMTR study.

Oren Pasvolsky et al.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Letter Oncology

Making clinical decisions based on measurable residual disease improves the outcome in multiple myeloma

Joaquin Martinez-Lopez et al.

Summary: Making clinical decisions based on MRD results in MM patients can lead to improved outcomes, as stopping or changing treatment based on MRD status can result in prolonged PFS.

JOURNAL OF HEMATOLOGY & ONCOLOGY (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

Ciltacabtagene autoleucel, a B-cell maturation antigendirected chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study

Jesus G. Berdeja et al.

Summary: The study aimed to evaluate the safety and clinical activity of cilta-cel in patients with relapsed or refractory multiple myeloma, and the results showed that cilta-cel treatment achieved good efficacy and safety with short treatment duration, deep response, and long duration of response.

LANCET (2021)

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Article Oncology

Pulse therapy with vincristine and dexamethasone for childhood acute lymphoblastic leukaemia (CCCG-ALL-2015) an open-label, multicentre, randomised, phase 3 non-inferiority trial

Wenyu Yang et al.

Summary: This study aimed to determine whether Vincristine plus dexamethasone pulses could be safely omitted in children with acute lymphoblastic leukaemia after 1 year of treatment. The results showed that the therapy could be omitted for children with low-risk leukaemia, but further studies are needed for those with intermediate-to-high-risk leukaemia.

LANCET ONCOLOGY (2021)

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Article Oncology

Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial

Philippe Moreau et al.

Summary: The CASSIOPEIA study compared daratumumab maintenance with observation only in newly diagnosed multiple myeloma patients, showing that daratumumab maintenance every 8 weeks for 2 years significantly reduced the risk of disease progression or death. Longer follow-up and other ongoing studies are needed to further understand the optimal daratumumab-containing post-ASCT maintenance treatment strategy.

LANCET ONCOLOGY (2021)

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Article Oncology

Minimal residual disease assessment by multiparameter flow cytometry in transplant-eligible myeloma in the EMN02/HOVON 95 MM trial

Stefania Oliva et al.

Summary: Minimal residual disease (MRD) detection by multiparameter flow cytometry (MFC) is a strong prognostic factor in assessing deep response in multiple myeloma patients, with MRD negativity significantly correlated with improved survival rates and reduced risk of progression or death. Lenalidomide maintenance therapy can further enhance the rate of MRD negativity.

BLOOD CANCER JOURNAL (2021)

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Article Oncology

NKG2D-CAR-transduced natural killer cells efficiently target multiple myeloma

Alejandra Leivas et al.

Summary: CAR-T-cell therapy has shown promising results against multiple myeloma, but with serious toxicities, while CAR-NK cells may have less toxicity against resistant myeloma cells. By using receptors like NKG2D, CAR-NK cells can exhibit broad target specificity. The study demonstrates the effective modification of autologous NKAE cells from MM patients to safely express a NKG2D-CAR, showing enhanced antimyeloma activity and supporting the development of NKG2D-CAR-NK-cell therapy for MM.

BLOOD CANCER JOURNAL (2021)

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Article Oncology

Sequential CD19/22 CAR T-cell immunotherapy following autologous stem cell transplantation for central nervous system lymphoma

Jiaying Wu et al.

Summary: The study treated 13 patients with CNSL using ASCT sequential CD19/22 CAR T-cell infusion. The results showed promising long-term efficacy and relatively manageable side effects of this treatment approach.

BLOOD CANCER JOURNAL (2021)

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Article Immunology

Efficacy of Humanized Anti-BCMA CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma Patients With and Without Extramedullary Disease

Haobin Deng et al.

Summary: This study observed the efficacy and safety of humanized anti-BCMA chimeric antigen receptor (CAR) T cell therapy in relapsed/refractory multiple myeloma patients with and without extramedullary disease. It was found that patients with extramedullary disease benefited in the short term from the therapy, although they experienced higher grades of cytokine release syndrome and immune effector cell-associated neurotoxic syndrome.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Hematology

Dynamics of minimal residual disease in patients with multiple myeloma on continuous lenalidomide maintenance: a single-arm, single-centre, phase 2 trial

Benjamin Diamond et al.

Lancet Haematology (2021)

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Article Oncology

Salvage Autologous Stem Cell Transplantation in Daratumumab-Refractory Multiple Myeloma

Lakshmi Yarlagadda et al.

Summary: Multiple Myeloma (MM) is a common cancer of the bone marrow that remains incurable despite advancements in therapy. While Daratumumab has improved survival rates, heavily pretreated patients who progress on this treatment have poor clinical outcomes. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) may be a viable treatment option for selected patients who are refractory to Daratumumab.

CANCERS (2021)

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Article Hematology

Post-Transplantation Cyclophosphamide for Graft-versus- Host Disease Prophylaxis in Multiple Myeloma Patients Who Underwent Allogeneic Hematopoietic Cell Transplantation: First Comparison by Donor Type. A Study from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation

Firoozeh Sahebi et al.

Summary: The retrospective study investigated the efficacy of using PT-Cy as GVHD prophylaxis in MM patients undergoing allo-HCT. The results showed similar incidence rates of acute and chronic GVHD among different donor types, and the use of PT-Cy had a positive impact on MM patients undergoing allo-HCT by significantly reducing the occurrence of GVHD.

TRANSPLANTATION AND CELLULAR THERAPY (2021)

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Article Hematology

Safety and Efficacy of Consolidation Therapy with Ipilimumab Plus Nivolumab after Autologous Stem Cell Transplantation

Alan P. Skarbnik et al.

Summary: Autologous hematopoietic stem cell transplantation (ASCT) is a standard treatment for hematologic malignancies, but disease progression remains a challenge. This Phase Ib trial investigated the effectiveness and safety of combined checkpoint inhibition therapy (CPIT) with ipilimumab and nivolumab post-ASCT for high-risk DLBCL, TCL, and MM patients. Results suggest CPIT is tolerable and may have clinical efficacy in certain subsets of disease, warranting further investigation based on biological rationale.

TRANSPLANTATION AND CELLULAR THERAPY (2021)

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Article Hematology

Haploidentical transplantation in patients with multiple myeloma making use of natural killer cell alloreactive donors

Catharina Van Elssen et al.

Summary: This study showed that in chemo-resistant multiple myeloma patients, NK cell KIR-mismatch is not superior to conventional transplantation, but this strategy may serve as a platform for new treatment concepts.

ANNALS OF HEMATOLOGY (2021)

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Article Biophysics

Minimal residual disease negativity and lenalidomide maintenance therapy are associated with superior survival outcomes in multiple myeloma

Dilan A. Patel et al.

BONE MARROW TRANSPLANTATION (2020)

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Article Oncology

Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study

Sagar Lonial et al.

LANCET ONCOLOGY (2020)

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Article Oncology

Response-adapted lenalidomide maintenance in newly diagnosed myeloma: results from the phase III GMMG-MM5 trial

Hartmut Goldschmidt et al.

LEUKEMIA (2020)

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Article Multidisciplinary Sciences

CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide

Sabarinath V. Radhakrishnan et al.

NATURE COMMUNICATIONS (2020)

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Review Oncology

Clinical Applications and Future Directions of Minimal Residual Disease Testing in Multiple Myeloma

Stefania Oliva et al.

FRONTIERS IN ONCOLOGY (2020)

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Article Hematology

Long-Term Follow-up of CALGB (Alliance) 100001: Autologous Followed by Nonmyeloablative Allogeneic Transplant for Multiple Myeloma

Sarah A. Holstein et al.

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION (2020)

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Article Hematology

Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial

Peter M. Voorhees et al.

BLOOD (2020)

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Article Biophysics

Long-term survival of 1338 MM patients treated with tandem autologous vs. autologous-allogeneic transplantation

Luciano J. Costa et al.

BONE MARROW TRANSPLANTATION (2020)

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Article Multidisciplinary Sciences

Systematically optimized BCMA/CS1 bispecific CAR-T cells robustly control heterogeneous multiple myeloma

Eugenia Zah et al.

NATURE COMMUNICATIONS (2020)

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Article Oncology

Deepening responses associated with improved progression-free survival with ixazomib versus placebo as posttransplant maintenance in multiple myeloma

Hartmut Goldschmidt et al.

LEUKEMIA (2020)

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Article Hematology

Prognostic Factors for Postrelapse Survival after ex Vivo CD34+-Selected (T Cell-Depleted) Allogeneic Hematopoietic Cell Transplantation in Multiple Myeloma

Alexandra Gomez-Arteaga et al.

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION (2020)

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Article Hematology

Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study

Michele Cavo et al.

LANCET HAEMATOLOGY (2020)

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Review Oncology

Development of CAR-T cell therapies for multiple myeloma

Nico Gagelmann et al.

LEUKEMIA (2020)

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Article Hematology

The Global State of Hematopoietic Cell Transplantation for Multiple Myeloma: An Analysis of the Worldwide Network of Blood and Marrow Transplantation Database and the Global Burden of Disease Study

Andrew J. Cowan et al.

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION (2020)

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Review Medicine, General & Internal

Emerging immunotherapies in multiple myeloma

Urvi A. Shah et al.

BMJ-BRITISH MEDICAL JOURNAL (2020)

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Article Hematology

Bortezomib, thalidomide, and dexamethasone with or without daratumumab for transplantation-eligible patients with newly diagnosed multiple myeloma (CASSIOPEIA): health-related quality of life outcomes of a randomised, open-label, phase 3 trial

Murielle Roussel et al.

Lancet Haematology (2020)

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Article Hematology

Bortezomib, thalidomide, and dexamethasone followed by double autologous haematopoietic stem-cell transplantation for newly diagnosed multiple myeloma (GIMEMA-MMY-3006): long-term follow-up analysis of a randomised phase 3, open-label study

Paola Tacchetti et al.

Lancet Haematology (2020)

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Article Hematology

Bortezomib, lenalidomide, and dexamethasone with or without elotuzumab in patients with untreated, high-risk multiple myeloma (SWOG-1211): primary analysis of a randomised, phase 2 trial

Saad Z Usmani et al.

Lancet Haematology (2020)

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Meeting Abstract Hematology

A Phase 1 First in Human (FIH) Study of AMG 701, an Anti-B-Cell Maturation Antigen (BCMA) Half-Life Extended (HLE) BiTE® (bispecific T-cell engager) Molecule, in Relapsed/Refractory (RR) Multiple Myeloma (MM)

Simon J. Harrison et al.

BLOOD (2020)

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Review Oncology

Autologous Stem-Cell Transplantation for Multiple Myeloma in the Era of Novel Therapies

Ricardo D. Parrondo et al.

JCO ONCOLOGY PRACTICE (2020)

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Article Hematology

Outcomes of Haploidentical Transplantation in Patients with Relapsed Multiple Myeloma: An EBMT/CIBMTR Report

Firoozeh Sahebi et al.

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION (2019)

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Article Hematology

Allogeneic transplantation of multiple myeloma patients may allow long-term survival in carefully selected patients with acceptable toxicity and preserved quality of life

Christine Greil et al.

HAEMATOLOGICA (2019)

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Review Oncology

Is lenalidomide the standard-of-care after an autotransplant for plasma cell myeloma?

Giovanni Barosi et al.

LEUKEMIA (2019)

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Article Multidisciplinary Sciences

CAR T cell trogocytosis and cooperative killing regulate tumour antigen escape

Mohamad Hamieh et al.

NATURE (2019)

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Article Hematology

Conditioning with busulfan plus melphalan versus melphalan alone before autologous haemopoietic cell transplantation for multiple myeloma: an open-label, randomised, phase 3 trial

Qaiser Bashir et al.

LANCET HAEMATOLOGY (2019)

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Article Medicine, General & Internal

Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma

Noopur Raje et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

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Article Multidisciplinary Sciences

leExploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma

Jie Xu et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

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Article Medicine, General & Internal

Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study

Philippe Moreau et al.

LANCET (2019)

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Article Hematology

γ-Secretase inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma

Margot J. Pont et al.

BLOOD (2019)

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Article Hematology

Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplant in multiple myeloma

Laura Rosinol et al.

BLOOD (2019)

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Article Hematology

Chimeric antigen receptor T-cell therapy for multiple myeloma: a consensus statement from The European Myeloma Network

Philippe Moreau et al.

HAEMATOLOGICA (2019)

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Article Oncology

Allogeneic transplantation in multiple myeloma: long-term follow-up and cytogenetic subgroup analysis

Stefan Knop et al.

LEUKEMIA (2019)

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Review Immunology

Granulocyte Colony-Stimulating Factor-Primed Unmanipulated Haploidentical Blood and Marrow Transplantation

Ying-Jun Chang et al.

FRONTIERS IN IMMUNOLOGY (2019)

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Article Hematology

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

Zhiling Yan et al.

LANCET HAEMATOLOGY (2019)

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Article Oncology

Autologous Transplantation, Consolidation, and Maintenance Therapy in Multiple Myeloma: Results of the BMT CTN 0702 Trial

Edward A. Stadtmauer et al.

JOURNAL OF CLINICAL ONCOLOGY (2019)

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Article Medicine, General & Internal

Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial

Meletios A. Dimopoulos et al.

LANCET (2019)

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Article Oncology

Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial

Mark T. Drayson et al.

LANCET ONCOLOGY (2019)

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Article Hematology

Rational design of a trimeric APRIL-based CAR-binding domain enables efficient targeting of multiple myeloma

Andrea Schmidts et al.

BLOOD ADVANCES (2019)

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Article Oncology

Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMGHD-4 trial

H. Goldschmidt et al.

LEUKEMIA (2018)

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Article Hematology

Autologous/Allogeneic Hematopoietic Cell Transplantation versus Tandem Autologous Transplantation for Multiple Myeloma: Comparison of Long-Term Postrelapse Survival

Myo Htut et al.

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION (2018)

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Article Hematology

The Role of Allogeneic Transplantation for Multiple Myeloma in the Era of Novel Agents: A Study from the Japanese Society of Myeloma

Koji Kawamura et al.

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION (2018)

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Article Hematology

Long-Term Results of Prophylactic Donor Lymphocyte Infusions for Patients with Multiple Myeloma after Allogeneic Stem Cell Transplantation

Maximilian Groeger et al.

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION (2018)

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Article Oncology

T Cells Genetically Modified to Express an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma

Jennifer N. Brudno et al.

JOURNAL OF CLINICAL ONCOLOGY (2018)

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Article Hematology

Myeloma escape after stem cell transplantation is a consequence of T-cell exhaustion and is prevented by TIGIT blockade

Simone A. Minnie et al.

BLOOD (2018)

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Article Hematology

Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR

Andrew Spencer et al.

HAEMATOLOGICA (2018)

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Article Oncology

A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma

Wan-Hong Zhao et al.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2018)

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Article Medicine, Research & Experimental

Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma

Alfred L. Garfall et al.

JCI INSIGHT (2018)

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Article Hematology

Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients

Bruno Paiva et al.

BLOOD (2016)

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Review Oncology

International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma

Shaji Kumar et al.

LANCET ONCOLOGY (2016)

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