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Functional Recovery Following Intensive Upfront Therapy in Multiple Myeloma Patients With Poor Performance Status: A Case Series.

Patients with newly diagnosed multiple myeloma (MM) may present with profound functional impairment due to high disease burden, and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 4 is often viewed as a barrier to intensive therapy despite potential reversibility. We report six newly diagnosed, bedbound MM patients (ECOG 4) treated with individualized multi-agent regimens incorporating proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies when feasible. Advanced features included extensive skeletal disease, renal dysfunction, hyperviscosity…

Long-term prognostic impact of chromosome 1 abnormalities in newly diagnosed multiple myeloma patients: a monocentric study.

The presence of chromosome 1 abnormalities in multiple myeloma (MM) has been included in the more recent prognostic staging system; however, the prognostic role of chromosome 1 abnormalities remains controversial. Thus, in this study we have investigated the prognostic role of chromosome 1 abnormalities in a cohort of newly diagnosed MM (NDMM), performing a retrospective monocentric analysis of 95 patients. Median follow up was 66 months for overall survival (OS) and progression free survival (PFS), and 55 months for time to next treatment (TTNT). Univariate analyses showed that 1q gain or amp…

Clinical Characteristics and Prognostic Analysis of Extramedullary Disease in Multiple Myeloma: A 15-Year Retrospective Cohort Study.

BACKGROUND: Extramedullary disease (EMD) in multiple myeloma (MM) is associated with poor prognosis, yet the clinical distinctions between bone-related EMD (bEMD) and soft tissue-associated EMD (sEMD) remain incompletely characterized. This study aimed to compare the clinical features and outcomes of bEMD versus sEMD and to develop a simple pre-treatment risk stratification tool using baseline clinical parameters. METHODS: We retrospectively analyzed 118 patients with MM and EMD treated at a single center from 2011 to 2025, including 72 bEMD and 46 sEMD cases. Baseline characteristics, labora…

Integrated Genomic and Epigenomic Analysis Reveals Epigenetic Plasticity in Disease Progression and Multidrug Resistance in Multiple Myeloma.

UNLABELLED: Multiple myeloma is marked by recurrent cytogenetic abnormalities and mutations that accumulate as the disease progresses. In this study, we sought to elucidate the transitions driving tumorigenesis and therapy resistance in multiple myeloma using a unique cohort of nearly 900 patients spanning premalignant to late-stage refractory multiple myeloma, comprehensively characterized at molecular and clinical levels. Waves of epigenetic dysregulation drove these critical transitions. In this paradigm, genomic and cytogenetic events unlocked epigenetic plasticity, reshaping multiple myel…

Характеристики, режим лечения и результаты лечения пациентов с истинной экстрамеуллярной множественной миеломой: реальный моноцентрический анализ.

Несмотря на значительные терапевтические достижения в области множественной миеломы (ММ), экстрамеуллярные заболевания (ЭМД) по-прежнему являются агрессивным подтипом, связанным с плохим прогнозом, в отношении которого отсутствует консенсус в отношении управления и не хватает специальных клинических испытаний. Мы провели ретроспективный одноцентральный анализ 86 пациентов с радиологически подтвержденными ЭМД, определяемыми как участие в мягких тканях без континуитета кости (отсечение данных в сентябре) 30, 2024). В группу входили пациенты с де ново ЭМД (n = 19, 22%) и вторичного ЭМД при рециди…

Programmed cell death protein 1 (PD-1) / programmed cell death ligand 1 (PD-L1) in multiple myeloma.

BACKGROUND: The bone marrow microenvironment in multiple myeloma (MM) is characterized by complex immune dysregulation involving multiple inhibitory pathways. Among these, the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis contributes to T-cell dysfunction; However, its isolated role within this multifactorial network remains incompletely defined. METHODS: This prospective observational study performed a cross-sectional immunophenotypic analysis of 39 newly diagnosed MM (NDMM) patients. PD-1 expression on T cells and PD-L1 expression on bone marrow (BM) pla…

Rapid regression of a bulky cranial lesion in high-risk multiple myeloma with isatuximab-based quadruplet induction.

A 77-year-old woman with newly diagnosed immunoglobulin (Ig)G-κ multiple myeloma presented with a massive cranial paraskeletal (PS) lesion (84 × 59 × 62 mm) compressing the occipital lobe. Fluorescence in situ hybridization of bone marrow aspirate revealed 1q21 gain and 17p deletion. Induction therapy with isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) was initiated to avoid emergent local intervention. The response was rapid; head computed tomography on day 28 showed an approximately 80% reduction in bidimensional measurements, with near-complete radiologic resolution by th…

Рециркуляция и теклистамаб в реанимированном миеломе: первый опыт у двух пациентов с обширной болезнью, прошедших курс интенсивной терапии.

Цель этой статьи состоит в том, чтобы рассказать о нашем первоначальном опыте использования двух пациентов с широко распространенной множественной миеломой, в том числе с рецидивом печени и менингелия, соответственно, с использованием двух специфической T-клеточной антерпрайзерной текклистамбы с соответствующей радиотерапией, включая рентгеновское облучение. Это ретроспективная оценка данных о пациентах в одном учреждении. Оба пациента ранее получали несколько линий системной терапии и радиотерапии по нескольким целевым показателям, в результате чего по завершении последних курсов в 2025 году …

Hyperviscosity Syndrome as a Rare Presentation of Immunoglobulin G Kappa Smoldering Multiple Myeloma Successfully Treated With Daratumumab.

Hyperviscosity syndrome (HVS) is an oncologic emergency most commonly associated with Waldenstrom macroglobulinemia and immunoglobulin (Ig)M paraproteinemia. Clinically, significant HVS in smoldering multiple myeloma (SMM), particularly IgG-associated disease without overt CRAB (hypercalcemia, renal insufficiency, anemia, and bone lesions) criteria, is exceedingly rare. We report a unique case of IgG kappa smoldering myeloma complicated by symptomatic HVS, manifesting with retinal hemorrhage, epistaxis, and gross hematuria, despite the absence of overt end-organ myeloma-defining events. A 70-y…

Ведомые АПРЕЛЬ БКМА/ТАКИ двойные целевые лиганды-наркотики для селективной и мощной терапии множественной миеломы.

Антиген созревания клеток B (BCMA) в значительной степени проявляется в злокачественных плазменных клетках и является идеальной терапевтической целью в множестве миеломы (MM). Однако эффективность лечения, ориентированного на BCMA, часто ограничивается регулированием деградации антигенов и выходом из опухоли. В этой связи мы представляем информацию о разработке двухцелевого лиганда-наркотика (НРС), использующего подпитывающий распространение лиган (АПРИЛ), естественного лиганда как для BCMA, так и для трансмембранового активатора, а также кальция-модулятора и циклофилина лиганда (TACI). Такая

Совпадение в аннотации оригинала
B-cell maturation antigen (BCMA) is highly expressed on malignant plasma cells and has emerged as an ideal therapeutic target in multiple myeloma (MM). However, the efficacy of BCMA-targeted therapies is often limited by antigen downregulation and tumor escape. Here, we report the design of a dual-targeted ligand-drug conjugate (LDC) leveraging a proliferati…

Daratumumab Plus Bortezomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma: Transplant-Ineligible Subgroup Analysis of CEPHEUS.

The phase III CEPHEUS trial (ClinicalTrials.gov identifier: NCT03652064) of patients with transplant-ineligible (TIE) or transplant-deferred newly diagnosed multiple myeloma (NDMM; N = 395) demonstrated improved overall minimal residual disease (MRD) negativity rates among patients achieving ≥complete response and progression-free survival (PFS) with daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd) versus VRd. We present efficacy and safety outcomes in the CEPHEUS TIE subgroup (N = 289; DVRd, n = 144; VRd, n = 145). Patients were either age 18-70 years with ≥1 comorbidity li…

Single-cell analysis of the multiple myeloma microenvironment after γ-secretase inhibition and CAR T-cell therapy.

Chimeric antigen receptor (CAR) T cells and bispecific antibodies targeting B-cell maturation antigen (BCMA) have significantly advanced the treatment of relapsed and refractory multiple myeloma. Resistance to BCMA-targeting therapies, nonetheless, remains a significant challenge. BCMA shedding by γ-secretase is a known resistance mechanism, and preclinical studies suggest that inhibition may improve anti-BCMA therapy. Leveraging a phase 1 clinical trial of the γ-secretase inhibitor (GSI), crenigacestat, with anti-BCMA CAR T cells (FCARH143), we used single-nuclei RNA sequencing and assay for …

Combining SKY92 gene expression profiling and FISH (according to R2-ISS) defines ultra-high-risk Multiple Myeloma.

The definition of high-risk (HR) multiple myeloma (MM) is still a matter of debate. We prospectively evaluated the HR detection using FISH in combination with SKY92 gene expression profiling in 258 MM patients (newly diagnosed [ND] MM: n = 109; relapsed/refractory [RR] MM: n = 149). HR SKY92 was significantly enriched in RRMM (57/121, 47.1%) compared with NDMM (17/95, 17.9%) (p < 0.0001). RRMM patients with HR SKY92 showed significantly shorter progression-free survival (PFS) (p < 0.0001) and overall survival (OS) (p < 0.0001) than SKY92 standard-risk (SR). In NDMM, HR SKY92 also indicated a s…

Inhibition of acyl-CoA synthetase long-chain isozymes decreases multiple myeloma cell proliferation and causes mitochondrial dysfunction.

Multiple myeloma (MM) is an incurable cancer of plasma cells with a 5-year survival rate of 59%. Dysregulation of fatty acid (FA) metabolism is associated with MM development and progression; however, the underlying mechanisms remain unclear. Herein, we explore the roles of long-chain fatty acid coenzyme A ligase (ACSL) family members in MM. ACSLs convert free long-chain fatty acids into fatty acyl-CoA esters and play key roles in catabolic and anabolic fatty acid metabolism. Analysis of the Multiple Myeloma Research Foundation (MMRF) CoMMpassSM study showed that high ACSL1 and ACSL4 expressio…

Perforated peptic ulcer disease as the initial presentation of previously unknown multiple myeloma and sickle cell anaemia.

Peptic ulcer disease (PUD) is a common cause of abdominal pain which can present acutely with gastrointestinal perforation. This report presents an exceptionally rare case of a patient whose presentation of perforated PUD heralded a new diagnosis of both multiple myeloma and sickle cell disease (SCD). Histological analysis of the ulcer tissue, following omental patch repair, did not demonstrate features of extramedullary myeloma or amyloid light chain deposition, two pathologies traditionally thought to drive PUD in this patient group. Instead, we suggest malignant hypercalcaemia stimulating g…

Deciphering response dynamics and treatment resistance from circulating tumor DNA after CAR T-cells in multiple myeloma.

Despite advances in treatments, multiple myeloma (MM) remains an incurable cancer where relapse is common. We developed a circulating tumor DNA (ctDNA) approach in order to characterize tumor genomics, monitor treatment response, and detect early relapse in MM. By sequencing 412 specimens from 64 patients with newly diagnosed or relapsed/refractory disease, we demonstrate the correlation between ctDNA and key clinical biomarkers, as well as patient outcomes. We further extend our approach to simultaneously track CAR-specific cell-free DNA (CAR-cfDNA) in patients undergoing anti-BCMA CAR T-cell…