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A myeloid-dormant metabolic transcriptome identifies a poor-prognosis subgroup in hyperdiploid multiple myeloma with targetable vulnerabilities.

Aberrant metabolism, a hallmark of cancer, reveals vulnerabilities across human tumors. Here, we demonstrate that transcriptomic alterations of metabolism-related genes (metabolic transcriptome) in multiple myeloma (MM), classify patients into six metabolic-transcriptional groups characterized by specific metabolic pathways and cytogenetic alterations, independent of currently described myeloma risk groups. Interestingly, hyperdiploid patients clustered into 2 groups (MM5 and MM6) with significantly distinct Progression-Free and Overall Survival. The MM5 group, with worse prognosis, showed a s…

Molecular Characterization of Mobilized Apheresis Hematopoietic Progenitor Cells Designated for Autologous Stem Cell Transplantation in Multiple Myeloma.

INTRODUCTION: Multiple myeloma is the second most common malignancy of the lymphoid system and accounts for about 2% of cancer deaths. Treatment generally consists of chemotherapy and autologous stem cell transplantation. Clinical trial results are equivocal as to whether autologous stem cell transplantation in the treatment of multiple myeloma prolongs overall survival. One possible etiology for this conundrum could be that the transplanted autologous stem cells may also contain residual tumor cells/tumor stem cells. METHODS: Residual autologous stem cells from patients undergoing stem cell …

Integrating MBMA and QSP to Identify Key Covariates and Predict Treatment Outcomes in Relapsed/Refractory Multiple Myeloma.

This study demonstrates the application of a model based meta analysis (MBMA) framework to characterize the safety and efficacy profiles of therapies in relapsed and refractory multiple myeloma (RRMM). Published clinical trial data were analyzed to evaluate the incidence of Grade ≥ 3 neutropenia and overall response rate (ORR), providing a quantitative foundation for model-informed drug development. The final model incorporated trial- and treatment-level covariates and was evaluated using visual predictive checks and predictive simulations. Results revealed increased neutropenia risk associate…

Т-клеточное истощение, вызванное терапией БиТЕ в множестве миэломы: снижение инфекционного риска с помощью свободных от лечения интервалов.

Множественная миелома (ММ), которая является высокоизлечимой, но до сих пор неизлечимой гематологической халатностью, потребовала постоянного наблюдения и лечения на протяжении всей жизни пациента. Новые классы терапии, такие, как химерик антиген-рецептор (CAR) T-клеток, которые представляют собой one- вливание времени, бросило вызов постоянной системе лечения. По сравнению с ранее известной стандартной терапией T-клеточная терапия CAR, а также биконкретная терапия T-клеточной терапии (BitE) были отмечены для того, чтобы вызвать более глубокие реакции, которые, как правило, являются устойчивым…

Daratumumab (Darzalex SC): Therapeutic area: Multiple myeloma in patients ineligible for autologous stem cell transplant: Reimbursement Review

What is multiple myeloma?Multiple myeloma is a cancer of plasma cells (the white blood cells that make immunoglobulins) found in the bone marrow. In 2025, approximately 4,285 people in Canada were newly diagnosed with multiple myeloma (NDMM). Among them, 2,125 people were not suitable for treatment with autologous stem cell transplant (ASCT) or did not plan to receive ASCT initially. The prognosis for these patients is poorer than for those who receive ASCT (median overall survival [OS] is 4.5 years compared to 8 to 10 years).What are the treatment goals and current treatment options for ndmm?…

Существенное бремя низкосортных инфекций у пациентов, которые лечатся с помощью T-клеток для лечения множественной миеломы.

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… Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387(6):495–505. doi: 10.1056/NEJMoa2203478. 2. Martin T, Usmani S, Cohen AD, et al. … Comparison of infectious complications with BCMA-directed therapies in multiple myeloma. Blood Cancer J. 2024;14(1):88. doi: 10.1038/s41408-024-01043-5. 19. Mohan M, Nagavally S, Dhakal B, et al. Risk of infections with B-cell maturation antigen-directed immunotherapy in multiple myeloma. …

Resumption of bone-modifying agents in relapsed multiple myeloma does not improve outcomes: A real-world analysis.

While bone-modifying agents (BMAs) are well-established components of frontline therapy in multiple myeloma, there are no data in the modern era to support their use in the relapsed setting. We conducted a retrospective analysis of US patients with relapsed/refractory multiple myeloma (RRMM) diagnosed between 2014 and 2023. Progression-free survival (PFS) and overall survival (OS) were analysed using Cox proportional hazards models adjusting for covariates including BMA receipt (BMA-received) versus not (BMA-deferred) at relapse. Of 1112 RRMM patients, 633 (56.9%) patients received BMAs follow…

Impact of Intensive Cyclophosphamide-Containing Multi-Agent Bridging Therapy on Outcomes after Idecabtagene Vicleucel in Multiple Myeloma.

Bridging therapy (BT) is frequently required during manufacturing of B-cell maturation antigen-directed chimeric antigen receptor T-cell (CAR-T) therapy in relapsed/refractory multiple myeloma. In patients with aggressive disease, intensive cyclophosphamide-containing multi-agent chemotherapy may be selected; however, its post-CAR-T impact remains uncertain, partly due to potential confounding by indication. To evaluate the impact of intensive cyclophosphamide-containing multi-agent BT on clinical outcomes after idecabtagene vicleucel infusion in a real-world setting. We conducted a retrospect…

METTL16 enhances proteasome inhibitor resistance in multiple myeloma by inhibiting eIF2α-PERK interaction and promoting PSMB5 translation.

Proteasome inhibitor (PI) resistance remains a major barrier in the treatment of multiple myeloma (MM), underscoring the urgent need to elucidate underlying mechanisms and identify actionable therapeutic targets. Here, we uncover METTL16 as a regulator of MM progression and PI sensitivity via an m6A methyltransferase activity-independent mechanism of translational control. Mechanistically, METTL16 overexpression is associated with altered PERK-eIF2α interaction and reduced eIF2α phosphorylation, accompanied by increased translation of key transcripts, including PSMB5 and CCND1. Consistently, t…

[Correlation between Serum AGR, LDH Levels and Efficacy of Induction Chemotherapy in Newly Diagnosed Multiple Myeloma Patients].

OBJECTIVE: To investigate the correlation between serum albumin-globulin ratio (AGR), lactate dehydrogenase (LDH) levels and the efficacy of induction chemotherapy in patients with newly diagnosed multiple myeloma (MM). METHODS: A total of 61 MM patients admitted to Maanshan Shiqiye Hospital from July 2021 to May 2024 were retrospectively collected as the observation group, and 61 healthy individuals who underwent physical examinations during the same period were enrolled as the control group. The differences in serum AGR and LDH levels between the two groups were compared. Pearson correlatio…

Tumor flare pain reaction following bispecific T-Cell engagers in multiple myeloma: a unique and underrecognized toxicity.

Not available.

IL-6-driven POU2AF1 and ELL2 are key regulators of multiple myeloma-distinct transcriptional and splicing programs.

Multiple myeloma (MM) is a plasma cell neoplasm that depends on the bone marrow (BM) microenvironment; however, the underlying mechanisms of epigenetic contribution to the pathogenesis of MM are incompletely understood. Here, we delineate epigenetically driven transcriptional and splicing regulation crucial for MM. We recharacterized the transcriptional program induced by interleukin 6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway by integrating chromatin immunoprecipitation sequencing, transcriptomic analyses, and CRISPR knockout screening, ident…

Mesoporous polydopamine-based biomimetic nanoplatform for immunotherapy of multiple myeloma by homologous targeting and systemic immune activation.

Photothermal therapy (PTT) not only directly eliminates tumors through its photothermal effects but also triggers a critical antitumor immun … membrane-coated CM@mPDA@Mn/CFZ nanosystem exhibits favorable biocompatibility. In a mouse model of multiple myeloma, the combination of this nanosystem with NIR irradiation showed significant synergistic therapeutic efficacy. It not only destroyed tumor cells directly, but it also stimulated dendritic cell (DC) maturation, CD3+ T cell activation, and cytotoxic T …

Dynamics of BCMA expression in patients with relapsed/refractory multiple myeloma receiving BCMA-directed CAR-T therapy.

There is limited systemic data on the dynamics of BCMA-target antigen expression with BCMA CAR-T at relapse. We analyzed 76 patients receiving standard-of-care BCMA-directed CAR-T who underwent real-time BCMA expression evaluation at baseline (n = 50), relapse (6), or both (20) using flow cytometry (FC) and/or immunohistochemistry (IHC). BCMA was universally expressed at baseline with significant heterogeneity in expression level. No concordance was seen between FC and IHC in categorizing high vs. low expression (Spearman: 0.07, Cohen kappa: 0). Plasma cell BCMA expression by FC correlated wit

Multiple myeloma burden and risk factors in China vs. high-income Asia Pacific: a macro-micro analysis.

BACKGROUND: Multiple myeloma (MM) presents a growing public health challenge in Asia, yet evidence on its epidemiology and risk factors in transitioning economies like China is limited. This study aimed to compare the disease burden, risk factors, and future trends of multiple myeloma between China and the High-Income Asia Pacific (HIC AP) region. METHODS: We conducted an integrated analysis combining data from the Global Burden of Disease (GBD) study 2023 (1993-2023) with a matched case-control study at a tertiary cancer center in China (2021-2025). The case-control component included 235 ne…

CD70-Targeting CAR NK Cells Overcome BCMA Downregulation and Improve Survival in High-risk Multiple Myeloma Models.

UNLABELLED: CD70 is highly expressed in many cancers, including multiple myeloma. We show in two cohorts of patients with multiple myeloma that CD70 is elevated in several high-risk disease categories and correlates with poor survival. These findings were validated using single-cell RNA sequencing, flow cytometry, and IHC. Moreover, we demonstrate the feasibility of targeting CD70 in myeloma using NK cells engineered with a chimeric antigen receptor (CAR) incorporating the CD70 cognate receptor CD27 and IL-15 (CAR27/IL-15). CAR27/IL-15 NK cells exerted potent in vitro and in vivo cytotoxicity …

CD8+CD38+ T cells identify functional high-risk multiple myeloma after autologous transplant: BMT CTN 0702 correlates.

Patients with multiple myeloma (MM) who experience early relapse (ER) within 24 months of autologous stem cell transplantation (ASCT) have inferior overall survival and represent a functionally high-risk (HR) subgroup. To investigate immune features of functionally HR MM, we performed immunohistochemistry (IHC) of the bone marrow and high-dimensional flow cytometry-based phenotyping of peripheral blood to evaluate the T-cell compartment of patients with MM at day 100 after ASCT. An initial IHC-based analysis of a cohort of patients with MM (n = 110) with long-term follow-up implicated CD3+PD-1…

High FCRL5 expression predicts poor treatment response and survival in newly diagnosed multiple myeloma: a retrospective study.

OBJECTIVES: Limited research is currently available regarding the prognostic value of Fc receptor-like 5 (FCRL5) in newly diagnosed multiple myeloma (NDMM). This study aimed to investigate the association of FCRL5 expression with treatment response and survival outcomes in NDMM patients, with a goal of providing insights for early risk stratification. METHODS: We retrospectively analyzed a cohort comprising 54 NDMM patients treated between January 2024 and January 2025 at a single center. Pretreatment FCRL5 expression was quantified by flow cytometry, and the median value (75.15%) was utilize…

Response-adapted lenalidomide-dexamethasone (LenDex) intensification after CyBorD induction for transplant-eligible multiple myeloma: the PIANO study.

PURPOSE: Combination therapy with novel agents is the standard initial treatment for transplant-eligible patients with newly diagnosed multiple myeloma. However, the benefit of additional induction therapy for insufficient response remains unclear. This multicenter prospective study investigated response-adapted intensification with lenalidomide and dexamethasone (LenDex) after cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in patients who did not achieve a very good partial response (VGPR) or better, followed by autologous stem cell transplantation (ASCT) and lenalidomide maintenanc…