The UK consensus supporting effective introduction of novel treatments for multiple myeloma in the National Health Service.

Introduction: Multiple myeloma (MM) is a relapsing, debilitating blood cancer which remains incurable despite advances in treatments. Patients typically receive multiple lines of treatment, to which they become refractory, thereby limiting treatment options. B-cell maturation antigen (BCMA) bispecific antibodies (BsAbs) represent a novel modality of treatment that has significant efficacy for relapsed or refractory patients.

Real-world practitioner perceptions of CARTITUDE-4 results for patients with previously treated multiple myeloma.

Introduction: Initially approved for the fifth-line or later therapeutic setting, the chimeric antigen receptor (CAR) T-cell regimen ciltacabtagene autoleucel (cilta-cel) was recently approved for second-line (2L) treatment in relapsed/refractory multiple myeloma (RRMM). Oncology practitioners use clinical trials to inform treatment, but real-world impressions and impact on practice are lacking. We aimed to determine whether presenting CARTITUDE-4 clinical trial data would impact real-world preferences/perceptions around CAR T-cell therapy.

Understanding ethnic inequalities in diagnostic intervals of cancer: a cohort study of patients presenting suspected cancer symptoms to general practitioners in England.

Background: UK Asian and black patients experience longer cancer diagnostic intervals - period between initial symptomatic presentation in primary care and cancer diagnosis.

Aim: To determine whether these differences are due to prolonged primary care intervals (period between first primary care presentation and secondary care referral), referral interval (period between referral and first secondary-care appointment) or secondary care interval (period between the first secondary care appointment and diagnosis).

Design And Setting: We conducted a cohort study of patients with seven common cancers (breast, lung, prostate, colorectal, oesophagogastric, myeloma, and ovarian), diagnosed after presenting symptoms in English primary care.

Exosomal tRF-1003 induces angiogenesis via regulating the HIF1α/VEGF signaling in multiple myeloma.

Background: Multiple myeloma (MM) remains a therapeutically challenging hematologic malignancy characterized by frequent relapse and disease progression. Angiogenesis regulated by non-coding RNAs plays a vital role in MM pathogenesis. Despite the potential clinical applications of tsRNAs, the specific mechanisms by which they contribute to MM progression, particularly through angiogenesis within the bone marrow microenvironment, remain elusive.

IRX-related homeobox gene MKX is a novel oncogene in acute myeloid leukemia.

Homeobox genes encode transcription factors which organize differentiation processes in all tissue types including the hematopoietic compartment. Recently, we have reported physiological expression of TALE-class homeobox gene IRX1 in early myelopoiesis restricted to the megakaryocyte-erythroid-progenitor stage and in early B-cell development to the pro-B-cell stage. In contrast, sister homeobox genes IRX2, IRX3 and IRX5 are aberrantly activated in the corresponding malignancies acute myeloid leukemia (AML) and B-cell progenitor acute lymphoid leukemia.

The current understanding of chimeric antigen receptor (CAR) T-cell therapy for older patients with relapsed or refractory large B-cell lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy has changed treatment landscape of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and more older patients have been treated with curative intent for R/R disease, including patients previously deemed unfit for autologous stem-cell transplant with a broader application of CAR T-cell therapy. Due to the unique CAR T-cell-related toxicity and special attention needed in treating older patients, optimal patient selection and management of CAR T-cell therapy in older patients are becoming more critical. More data are emerging in the field; multiple approaches, such as geriatric and frailty assessment and multi-disciplinary work with geriatrics, are being studied for CAR T-cell therapy application.

Light-Chain Myeloma Presented as Osseus Tumors: A Case Report.

Light-chain multiple myeloma (LCMM) is a rare subtype of plasma cell neoplasm, usually linked to kidney involvement and lytic bone lesions. However, case presents as osseus tumors are very uncommon. A 63-year-old male patient complained of persistent rib pain.

Increased CSN5 expression enhances the sensitivity to lenalidomide in multiple myeloma cells.

Lenalidomide (LEN) is commonly used as an effective therapeutic agent for multiple myeloma (MM). However, in some patients, primary resistance to LEN is observed, the mechanisms of which remain poorly understood. In this study, we combined a LEN sensitivity assay with proteomics data from 15 MM cell lines to identify protein expression profiles associated with primary LEN resistance.

T cell margination: investigating the detour of T cells following forimtamig treatment in humanized mice.

T cell bispecific antibodies (TCBs) are a promising new class of therapeutics for relapsed/refractory multiple myeloma. A frequently observed, yet incompletely understood effect of this treatment is the transient reduction of circulating T cell counts, also known as T cell margination (TCM). After administration of the GPRC5D-targeting TCB forimtamig (RG6234), TCM occurred in patients and correlated with cytokine release and soluble B cell maturation antigen decrease.

Role of Imaging in Multiple Myeloma: A Potential Opportunity for Quantitative Imaging and Radiomics?

Multiple myeloma (MM) is the second most prevalent hematologic malignancy, particularly affecting the elderly. The disease often begins with a premalignant phase known as monoclonal gammopathy of undetermined significance (MGUS), solitary plasmacytoma (SP) and smoldering multiple myeloma (SMM). Multiple imaging modalities are employed throughout the disease continuum to assess bone lesions, prevent complications, detect intra- and extramedullary disease, and evaluate the risk of neurological complications.

Clinical Characteristics, Cytogenetic Risks, and Prognoses of Young Multiple Myeloma Patients in the Era of Novel Therapies.

In recent years, there have been significant advances in the understanding and treatment of multiple myeloma (MM). Despite this progress, there is still limited information on the disease in patients aged 50 or younger, including the impact of young age on disease characteristics, treatment, and outcome. In this retrospective study, we analyzed 68 newly diagnosed MM patients aged ≤ 50 years (y) who had undergone at least one peripheral blood stem cell transplantation (PBSCT).

Multiple Myeloma Cells with Increased Proteasomal and ER Stress Are Hypersensitive to ATX-101, an Experimental Peptide Drug Targeting PCNA.

: To examine the regulatory role of PCNA in MM, we have targeted PCNA with the experimental drug ATX-101 in three commercial cell lines (JJN3, RPMI 1660, AMO) and seven in-house patient-derived cell lines with a more primary cell-like phenotype (TK9, 10, 12, 13, 14, 16 and 18) and measured the systemic molecular effects. : We have used a multi-omics untargeted approach, measuring the gene expression (transcriptomics), a subproteomics approach measuring mainly signalling proteins and proteins in complex with these (signallomics) and quantitative metabolomics. These results are supplemented with traditional analysis, e.

Targeted Delivery of c(RGDfk)-Modified Liposomes to Bone Marrow Through In Vivo Hitchhiking Neutrophils for Multiple Myeloma Therapy.

Multiple myeloma (MM) is a prevalent bone marrow disorder. The challenges in managing MM include selecting chemotherapy regimens that effectively modulate the myeloma microenvironment and delivering them to the bone marrow with high efficacy and minimal toxicity. Herein, a novel bone marrow targeting strategy using c(RGDfk) peptide-modified liposomes loaded with chemotherapeutics is developed, which can specifically recognize and hitchhike neutrophils following systemic administration, capitalizing on their natural aging process to facilitate precise drug delivery to the bone marrow, thus minimizing off-target effects.

Expression profile of Bcl-2 family proteins in newly diagnosed multiple myeloma patients.

Antiapoptotic Bcl-2 family proteins are involved in myeloma cell survival. To date, their expression in multiple myeloma (MM) patients has mostly been analyzed at the RNA level. In the present study, we quantified for the first time the protein expression of the Bcl2-family members using a capillary electrophoresis immunoassay in 120 newly diagnosed MM patients, aged ≤65 years, treated in the context of the PETHEMA/GEM2012 study.

Vitamin D in patients with low tumor-burden indolent non-Hodgkin lymphoma treated with rituximab therapy (ILyAD): a randomized, phase 3 clinical trial.

Background: There is a significant association between low vitamin D levels at diagnosis of indolent B-cell lymphomas and inferior overall survival (OS). To determine whether supplemental vitamin D improves event-free survival (EFS) in these patients, we conducted a comparative double-blind study of vitamin D vs. placebo.

Extra-medullary Plasmacytomas: A Case Series of Rare Hematological Tumors.

Solitary plasmacytoma is a rare malignant tumor belonging to the family of plasma cell proliferation. It accounts for a small portion of plasma cell tumors and remains a rare condition. We report three cases of rare extraosseous plasmacytomas in young patients.

The Synchronous Diagnosis of Multiple Myeloma (MM) and Chronic Myeloid Leukemia (CML).

The synchronous presentation of chronic myeloid leukemia (CML) and multiple myeloma (MM) is extremely rare. CML is a myeloproliferative neoplasm originating from an abnormal pluripotent hematopoietic stem cell. It is associated with the - fusion gene located on the Philadelphia chromosome.

Anti-BCMA and GPRC5D bispecific antibodies in relapsed/refractory primary plasma cell leukemia: a case report.

Plasma cell leukemia (PCL) is an aggressive and high-risk variant of multiple myeloma (MM) with a very poor prognosis. Given its rarity and aggressiveness, there is a lack of clinical trials testing the efficacity of novel therapies in these patients. New immune approaches such as B-cell maturation antigen (BCMA) and G protein-coupled receptor, family C, group 5, member D (GPRC5D) -targeting agents, including chimeric antigen receptor (CAR) T-cells and bispecific antibodies could play a role in PCL treatment.

A real-world study on the impact of infection load on mortality in multiple myeloma patients in Finland.

Infections are a clinically significant cause of mortality in multiple myeloma (MM) patients. The high number of infections in MM patients is due to the immunosuppressive effects of the disease itself as well as treatment-related immunosuppression. In this real-world evidence (RWE) study, we used several nationwide healthcare registries of Finland to investigate the effect of infection load on mortality in MM patients during 1997-2021.

Comprehensive Review of Bispecific Antibody Constructs In Multiple Myeloma: Affinities, Dosing Strategies and Future Perspectives.

Despite significant advancements, multiple myeloma (MM) remains incurable, and there is still a pressing need for new therapeutic strategies with highly selective mechanisms of action and balanced off-target toxicity. In recent years, the development of "off-the-shelf" bispecific antibodies (bsAbs) has significantly enhanced our ability to treat relapsed or refractory MM. Teclistamab, elranatamab (both BCMA × CD3), and talquetamab (GPRC5D × CD3) are approved for treating MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.