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Mechanisms of resistance against T-cell engaging bispecific antibodies in multiple myeloma: implications for novel treatment strategies.

Off-the-shelf T-cell-redirecting bispecific antibodies targeting BCMA, GPRC5D, and FcRH5 have high activity in multiple myeloma with a manageable toxicity profile. However, not all patients respond to bispecific antibodies and patients can develop bispecific antibody resistance after an initial response. Mechanisms that contribute to bispecific antibody resistance are multifactorial and include tumour-related factors, such as high tumour burden, expression of T-cell inhibitory ligands, and antigen loss. Resistance due to antigen escape can be prevented by simultaneously targeting two tumour-as…

Assessment of inter- and intraobserver agreement for META score in distinguishing osteoporotic from multiple myeloma vertebral fractures.

PURPOSE: To conduct an independent assessment of inter- and intraobserver agreement for the META score as a tool for differentiating osteoporotic vertebral fractures and multiple myeloma vertebral fractures. METHODS: This is a retrospective observational study. The magnetic resonance imaging analysis was made by two independent spinal surgeons. We designated a Subjective assessment, in which the surgeon should establish a diagnostic classification for each vertebral fracture based on personal experience: secondary to osteoporosis, categorized as a benign vertebral fracture (BVF), or attribute…

Pericapsular nerve group block followed by regional anesthesia for pathological fracture fixation in a multiple myeloma patient.

UNLABELLED: Appropriate anesthetic technique for fracture fixation in multiple myeloma is crucial in minimizing perioperative complications. The use of pericapsular nerve group block followed by spinal anesthesia for the operative management of pathological fracture in multiple myeloma patient along with proper pre- and postanesthetic care ensures better outcome for the patient. ABSTRACT: Multiple myeloma is a malignant plasma cell disease that often presents with anemia, renal failure, hyperkalemia and osteolytic bone lesions. The advancements in drug therapy of multiple myeloma have prolong…

Случаи и предотвращение событий, связанных со скелетом, у многих пациентов, страдающих миэломой: опыт реальной жизни населения.

Новейшее лечение в миеломе (ММ) может повлиять на частотность событий, связанных со скелетом (СРП). Мы ставили перед собой цель изучить распространенность SRE и профилактическое использование остеокластных ингибиторов (ОИ) в группе пациентов ММ в эпоху современного лечения. В этом ретроспективном исследовании реального мира мы включили 199 пациентов с диагнозом MM в период с января 1, 2010, и декабрь 31, 2019, с последующими мерами на Сент-Луисе. Больница Университета Олава. Данные были взяты из регистра миеломы в центральной части Норвегии. ИСП произошли в 46% пациентов на базовом уровне и 55

Совпадение в аннотации оригинала
Novel treatments in multiple myeloma (MM) could influence the incidence of skeletal-related events (SREs). We aimed to examine the incidence of SRE and the preventive use of osteoclast inhibitors (OIs) in a cohort of MM patients in the era of modern treatment. In this real-world retrospective study, we included 199 patients with a diagnosis of MM between Jan…

Моноклональная антитела в Смолдингах Множественная Миелома и Моноклональная Гаммопатия Неопределенной Значимости: Текущий статус и будущие направления.

Моноклональные антитела (MoAbs), предназначенные для нескольких клеточных рецепторов, значительно улучшили прогноз множественных миелом (MM). Их высокая эффективность и безопасность поднимают вопрос о том, влияет ли на естественный ход болезни более раннее терапевтическое вмешательство в моноколональную гаммопатию неопределенного значения (МГУС) и задушающую миелому (ШМ). ММ предшествует клинически признанным условиям, таким, как МГУС и SMM. В рамках многочисленных исследований изучается биология заболеваний и иммунный профиль SMM и MGUS, с тем чтобы разгадать сложную связь между иммуноконтрол

Совпадение в аннотации оригинала
Monoclonal antibodies (MoAbs) targeting several cellular receptors have significantly improved the prognosis of multiple myeloma (MM). Their high effectiveness and safety raise the question of whether earlier therapeutic intervention in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) influences the natural cour…

Accelerating Healing and Relieving Pain: High-Intensity Laser Therapy for Paraneoplastic Cutaneous Vasculitis Associated with Multiple Myeloma.

BACKGROUND Leukocytoclastic vasculitis (LCV) is an atypical form of cutaneous paraneoplastic manifestation. Its association with multiple myeloma (MM) is even rarer and is associated with poor prognosis and short survival, regardless of the therapy instituted. Different treatment approaches are necessary. We present a case in which LCV was the first manifestation of MM, and high-intensity laser therapy (HILT) was used as an option to accelerate healing and control pain. CASE REPORT A 76-year-old woman presented with pain and paresthesia in her lower limbs, associated with palpable purpura. The…

Preclinical delayed toxicity studies of BCMA CAR T-cell injection in B-NDG mice with multiple myeloma.

PURPOSE: Based on the efficacy data from the previous study of B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell injection, we further examined the delayed toxicity for 8 weeks after a single dose of BCMA CAR T-cell injection to observe possible toxic reactions. METHODS: B-NDG mice transplanted with multiple myeloma (MM) cells were given a single dose of BCMA CAR T-cell injection at two dosages or human normal T cells and then subjected to examinations including clinical signs, weight and food intake measurements, haematology, blood biochemical analysis, cytokine assay, …

Brain Nocardiosis Mimicking Intracerebral Invasion on 68 Ga-Pentixafor PET/CT in a Patient With Multiple Myeloma.

Brain nocardiosis is an uncommon but severe disease associated with high mortality. We present a case of brain nocardiosis with elevated tracer uptake on both 68 Ga-pentixafor and 18 F-FDG PET/CT, mimicking intracerebral invasion of multiple myeloma. This case demonstrates that nocardiosis should be considered in the differential diagnosis of brain lesions found on PET/CT with increased tracer accumulation in immunocompromised patients.

Prognostic value of RGS1 and mTOR Immunohistochemical expression in Egyptian multiple myeloma patients; A single center study.

INTRODUCTION: Prognostic factors in plasma cell myeloma were proved to be related to signaling pathways and associated transcription factors. RGS1 and mTOR were known to play an important role in the pathogenesis of multiple myeloma. The aim of the study was to evaluate the expression and the prognostic value of RGS1 and mTOR and their relation to clinical as well as other diagnostic criteria in multiple myeloma. PATIENTS AND METHODS: The present study included 44 denovo Myeloma patients, recruited from the Medical Oncology Department, National Cancer Institute, Cairo University. Detection of…

Exploiting big data survival information to unify risk-stratification related, adaptive immune receptor parameters for multiple myeloma.

With the improvement of treatment options, multiple myeloma related life expectancy has been prolonged, but the disease remains largely incurable. Immunotherapy is a growing field that shows promise in advancements for treatment, and recent work has demonstrated an opportunity to use immune receptor, complementarity determining region-3 (CDR3)-candidate antigen chemical complementarity scores to identify survival distinctions among subgroups of patients. Here, we have applied the complementarity scoring algorithm to identify multiple myeloma related, CDR3-cancer testis antigen (CTA) relationsh…

Isatuximab Plus Carfilzomib and Dexamethasone in East Asian Patients With Relapsed Multiple Myeloma: Updated IKEMA Subgroup Analysis.

BACKGROUND: The Phase 3 IKEMA study (NCT03275285) demonstrated isatuximab (Isa) in combination with carfilzomib (K) and dexamethasone (d) significantly improved progression-free survival (PFS) in patients with relapsed multiple myeloma (MM) compared with Kd. A post-hoc analysis of East Asian patients in IKEMA evaluated the efficacy and safety of Isa-Kd versus Kd in this population and was previously published. PATIENTS AND METHODS: Patients with relapsed MM who had received 1 to 3 prior lines of therapy were randomized 3:2 to receive Isa-Kd or Kd. The primary endpoint was PFS, and key seconda…

AL Amyloidosis and Multiple Myeloma: A Complex Scenario in Which Cardiac Involvement Remains the Key Prognostic Factor.

Monoclonal gammopathies (MGs) are a wide range of diseases that may evolve or progress over time. Comorbidity plays a critical role in this setting. The co-occurrence of two MGs is not a rare event. The evidence on the association of systemic light chain (AL) amyloidosis and multiple myeloma (MM) is scarce and controversial. Herein we aim to address this topic in a large series of patients of a referral center. All consecutive AL amyloidosis patients treated at our center from January 2005 to April 2023 were prospectively enrolled in a clinical and epidemiological registry. 141 patients diagno…

HRAS mutation positive multiple myeloma in the type 2 CALR mutation positive essential thrombocythemia: A case report.

Out of BCR-ABL negative myeloproliferative neoplasm (MPNPh- ) patients, 3%-14% display a concomitant monoclonal gammopathy of unknown significance (MGUS). In most cases, the diagnosis of plasma cell dyscrasia is either synchronous with that of MPNPh- or occurs later on. We present a 50-year-old patient with type 2 CALR Lys385Asnfs*47 mutation positive essential thrombocythemia (ET) who developed symptomatic multiple myeloma (MM) 13 years after the diagnosis of ET during PEG-INF2α treatment. The NGS study performed at the time of the MM diagnosis revealed the HRAS Val14Gly/c.41T〉G mutation and …

Design and synthesis of 1H-benzo[d]imidazole selective HDAC6 inhibitors with potential therapy for multiple myeloma.

Pan-HDAC inhibitors exhibit significant inhibitory activity against multiple myeloma, however, their clinical applications have been hampered by substantial toxic side effects. In contrast, selective HDAC6 inhibitors have demonstrated effectiveness in treating multiple myeloma. Compounds belonging to the class of 1H-benzo[d]imidazole hydroxamic acids have been identified as novel HDAC6 inhibitors, with the benzimidazole group serving as a specific linker for these inhibitors. Notably, compound 30 has exhibited outstanding HDAC6 inhibitory activity (IC50 = 4.63 nM) and superior antiproliferativ…

B-cell maturation antigen chimeric antigen receptor-T therapy alleviated heart failure in patients with multiple myeloma.

Patients with multiple myeloma (MM) are likely to achieve poor therapeutic response when organs are involved. We produced anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cells, which are in a trial for patients with relapsed/refractory MM. One enrolled patient developed severe heart failure, highly suspected as light chain cardiac amyloidosis. He exhibited increased N-terminal pro-brain natriuretic peptide with a peak of 32 299 ng/mL and heart failure with an ejection fraction of 30%. Anti-BCMA CAR-T cells were administered following lymphodepletion. The patient achieve…

The Impact of Renal Impairment in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation With Melphalan Conditioning.

BACKGROUND: There are no standard renal dose adjustments for melphalan conditioning for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients. The objective of this study was to evaluate the effect of melphalan dosing and chronic kidney disease (CKD) on transplant-related outcomes, progression-free survival (PFS), and overall survival (OS). METHODS: A retrospective chart review was performed, and MM patients who underwent ASCT between February 2016 and September 2021 were included. Melphalan 200 mg/m2 (Mel200) or 140 mg/m2 (Mel140) was administered. The cohort was divi…

Red cell distribution width, neutrophil lymphocyte ratio and interleukin 10 are good prognostic markers in multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is still an incurable disease so we need to continue developing new diagnostic and prognostic options for its management. There are multiple prognostic factors for MM, but most of them are costly and time consuming. Hence comes the urge to identify bed side and low cost prognostic tools, that is why this study was aiming to identify in Egyptian MM patients. MATERIALS AND METHODS: The study was carried on 60 newly diagnosed multiple myeloma patients and 20 age and sex matched healthy individuals as controls. Studied subjects were subdivided into two groups: Gr…

Chimeric antigen receptor and bispecific T-cell engager therapies in multiple myeloma patients with prior allogeneic transplantation.

Chimeric antigen receptor T-cell (CAR-T) therapy and bispecific T-cell engagers (BsAb) have emerged as promising immunotherapeutic modalities in patients with relapsed and/or refractory multiple myeloma (RRMM). However, there is limited data on the safety and efficacy of CAR-T and BsAb therapies in MM patients with a prior history of allogeneic transplantation (allo-HCT). Thirty-three MM patients with prior allo-HCT received CAR-T (n = 24) or BsAb (n = 9) therapy. CAR-T therapy demonstrated an ORR of 92% (67% ≥ CR), and 73% were MRD negative. BsAb therapy resulted in an ORR of 44% (44% ≥ CR) a…

[Establishment of Patient-Derived Xenograft (PDX) Zebrafish Model of Multiple Myeloma and Its Application in Drug Screening].

OBJECTIVE: To establish a MM patient-derived tumor xenograft model (MM-PDX) in zebrafish, and to evaluate the anti-myeloma activity of indirubin-3'-monoxime(I3MO) using this model. METHODS: Zebrafish embryos 2 days after fertilization were transplanted with fluorescence labeled myeloma primary tumor cells, the survival of primary tumor cells in zebrafish was observed at 0,16 and 24 hours after cell injection. The zebrafish embryos after tumor cell transplantation were randomly divided into control group, BTZ treatment and I3MO treatment group. Before and 24 hours after treatment with BTZ and