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CAR T-Cell Therapy for Patients with Multiple Myeloma: Current Evidence and Challenges.

The therapeutic landscape of multiple myeloma (MM) has benefited from an emergence of novel therapies over the last decade. By inducing T-cell kill of target cancer cells, chimeric antigen receptor (CAR) T-cell therapies have improved outcomes of patients with hematologic malignancies. B-cell maturation antigen (BCMA) is the current target antigen of choice for most CAR T-cell products under investigation for MM. However, their shortcomings deal with logistical and clinical challenges, including limited availability, manufacturing times, and toxicities. This article provides an overview of rec

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… CAR-T-OPENIA: chimeric antigen receptor T-cell therapy-associated cytopenias. eJHaem . 2022;3(Suppl. 1):32–38. 39. Busca A, Salmanton-Garcia J, Corradini P, et al. COVID-19 and CAR T cells: a report on current challenges and future directions from the EPICOVIDEHA survey by EHA-IDWP. …

MUKnine OPTIMUM protocol: a screening study to identify high-risk patients with multiple myeloma suitable for novel treatment approaches combined with a phase II study evaluating optimised combination of biological therapy in newly diagnosed high-risk multiple myeloma and plasma cell leukaemia.

INTRODUCTION: Multiple myeloma (MM) is a plasma cell tumour with over 5800 new cases each year in the UK. The introduction of biological therapies has improved outcomes for the majority of patients with MM, but in approximately 20% of patients the tumour is characterised by genetic changes which confer a significantly poorer prognosis, generally termed high-risk (HR) MM. It is important to diagnose these genetic changes early and identify more effective first-line treatment options for these patients. METHODS AND ANALYSIS: The Myeloma UK nine OPTIMUM trial (MUKnine) evaluates novel treatment

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… Introduction Multiple myeloma (MM) is a clonal disorder of plasma cells which accumulate in the bone marrow leading to cytopenias, bone resorption, renal impairment, infection and the production of a monoclonal protein. 1 MM represents 1.5% of all malignant diseases, with an incidence of 9/100 000 per …

Multiple Myeloma and Thrombosis: Prophylaxis and Risk Prediction Tools.

Thromboembolism in multiple myeloma (MM) patients remains a common complication that renders the optimization of our thromboprophylaxis practice necessary. This review aims to make clear the need for the development of more accurate risk assessment tools and means of thrombosis prevention. Current clinical practice is guided by available guidelines published by the IMWG in 2014, but the extent to which these are implemented is unclear. Recently, several groups developed clinical scores for thrombosis risk in MM in an attempt to improve risk stratification, but these have not been validated or

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… Most clinicians favor LMWH compared to warfarin particularly for patients with cyclical cytopenias, who are at higher bleeding risk. Patient compliance given the parenteral method of administration remains an issue. …

What the Intensivists Need to Know About Critically Ill Myeloma Patients

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… Factors that make oral anticoagulation less ideal is drug-drug interaction and unreliable therapeutic levels resulting from patient-related malnutrition, infection, and drug holds from cytopenias. Once full anticoagulation is attained, the immunomodulator can be reintroduced. …

Enasidenib in the treatment of relapsed/refractory acute myeloid leukemia: an evidence-based review of its place in therapy.

Introduction: Acute myeloid leukemia (AML) remains a disease with high mortality, especially for older patients and those with relapsed/refractory (R/R) disease. With recent advances in molecular testing, targeting particular leukemogenic mutations such as those occurring in isocitrate dehydrogenase (IDH) became possible. Enasidenib is a new small-molecule inhibitor of mutant isocitrate dehydrogenase-2 (IDH2). Aim: The objective of this article is to review the evidence for the use of enasidenib in R/R AML, as well as to outline future directions of enasidenib therapy. Evidence Review: Enaside

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… Introduction Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with high mortality, characterized by excess clonal myeloid blasts that infiltrate the bone marrow and other tissues, as well as related cytopenias. …

The Production Processes and Biological Effects of Intravenous Immunoglobulin.

Immunoglobulin is a highly diverse autologous molecule able to influence immunity in different physiological and diseased situations. Its effect may be visible both in terms of development and function of B and T lymphocytes. Polyclonal immunoglobulin may be used as therapy in many diseases in different circumstances such as primary and secondary hypogammaglobulinemia, recurrent infections, polyneuropathies, cancer, after allogeneic transplantation in the presence of infections and/or GVHD. However, recent studies have broadened the possible uses of polyclonal immunoglobulin showing that it ca

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… This is the case in peripheral autoimmune cytopenias (e.g., idiopathic thrombocytopenic purpura). In such situations, the saturation of Fc receptors by IVIg leads to decreased cellular destruction as a consequence of Fc-mediated phagocytosis of antibody-coated cells [ 19 , 62 , 63 ]. 4.2. …

Challenges in the Role of Gammaglobulin Replacement Therapy and Vaccination Strategies for Hematological Malignancy.

Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are prone to present with antibody production deficits associated with recurrent or severe bacterial infections that might benefit from human immunoglobulin (Ig) (IVIg/SCIg) replacement therapy. However, the original IVIg trial data were done before modern therapies were available, and the current indications do not take into account the shift in the immune situation of current treatment combinations and changes in the spectrum of infections. Besides, patients affected by other B cell malignancies present with similar i

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… Delayed-onset peripheral blood cytopenia after rituximab: frequency and risk factor assessment in a consecutive series of 77 treatments. Leuk Lymphoma (2006) 47(6):1013–7. 10.1080/10428190500473113 98. Gea-Banacloche JC. Rituximab-associated infections. …

Targeting hedgehog signaling in myelofibrosis and other hematologic malignancies.

Treatment of myelofibrosis (MF), a BCR-ABL-negative myeloproliferative neoplasm, is challenging. The only current potentially curative option, allogeneic hematopoietic stem cell transplant, is recommended for few patients. The remaining patients are treated with palliative therapies to manage MF-related anemia and splenomegaly. Identification of a mutation in the Janus kinase 2 (JAK2) gene (JAK2 V617F) in more than half of all patients with MF has prompted the discovery and clinical development of inhibitors that target JAK2. Although treatment with JAK2 inhibitors has been shown to improve sy

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… MF is characterized by stem cell–derived clonal myeloproliferation, abnormal cytokine expression, bone marrow fibrosis, cytopenias, extramedullary hematopoiesis (eg, splenomegaly), cachexia, and constitutional symptoms including night sweats, fevers, weight loss, and fatigue [ 3 - 5 ]. …

Molecular Inhibitors of Growth Signals

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The 44th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians Oral Session

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… Asymptomatic viral reactivations (CMV and/or adenovirus) were seen in 3 patients and resolved with antiviral therapy. 3/7 patients developed prolonged G4 cytopenia. 5 out of 7 patients achieved molecular remission (MRD-ve) at D28, 1 had refractory disease at D28 and 1 died at D15. …

ESCP 36th European Symposium on Clinical Pharmacy ‘Implementing Clinical Pharmacy in Community and Hospital Settings: Sharing the Experience’, Istanbul, Turkey 25–27 October 2007; Abstracts

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… prescriptions in the department of conventional hematology at Nantes University Hospital PT-188 Pharmacotherapy of first-episode psychosis in the psychiatry clinics of the north estonia regional hospital (NERH) and the Tartu University Hospital (TUH) PT-195 Assessment of rituximab use in refractory autoimmune cytopenia …

Exercise-modulated IL-6 in cancer cachexia: molecular mechanisms and therapeutic potential.

BACKGROUND: Cancer cachexia is a multifactorial metabolic syndrome marked by progressive skeletal muscle wasting, systemic inflammation, reduced quality of life, and poor clinical outcomes. Interleukin-6 (IL-6) is a central mediator in cachexia pathophysiology, driving inflammatory signaling, catabolic metabolism, and muscle atrophy. However, IL-6 also rises transiently during exercise, where it exerts beneficial metabolic and anti-inflammatory effects, highlighting the context-dependent nature of IL-6 signaling. MAIN BODY: This review summarizes current knowledge on the regulation and functio

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… focus on optimizing treatment sequencing (e.g., initiating IL-6 blockade during acute catabolic phases, followed by supervised exercise as tolerance improves), biomarker-guided patient selection (e.g., based on baseline CRP, IL-6, or STAT3 activity), and vigilant safety monitoring for infections and cytopenias … Practical safeguards include pre-exercise screening, withholding sessions during fever or severe cytopenias, and close coordination with the oncology team. …

Immunoglobulin A Nephropathy: Molecular Pathogenesis and Targeted Therapy.

Immunoglobulin A nephropathy (IgAN), the most prevalent primary glomerulonephritis globally, is characterized by mesangial IgA deposition and heterogeneous clinical trajectories. Historically, management relied on renin-angiotensin system inhibition and empirical immunosuppression, yet high lifetime kidney failure risk persists despite optimized care. This review synthesizes advances in molecular pathogenesis, highlighting how the traditional multi-hit hypothesis-while foundational for targeted therapy development-fails to capture IgAN's recurrent, self-amplifying nature. We introduce the "spi

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… Early‐phase IgAN trials demonstrate proteinuria reductions (40–60% with felzartamab) but reveal significant toxicity—including cytopenias, opportunistic infections, and cardiotoxicity—offsetting potential benefits while biopsy efficacy awaits confirmation. … Early studies in IgAN have shown promising results in reducing proteinuria [ 278 , 279 , 280 , 281 ], but cytopenias and neuropathy limit long‐term use. Larger clinical trials are needed to establish the efficacy and safety of this approach in the long‐term management of the disease. …

Novel agents and regimens for hematological malignancies: recent updates from 2020 ASH annual meeting.

Antibodies and chimeric antigen receptor-engineered T cells (CAR-T) are increasingly used for cancer immunotherapy. Small molecule inhibitors targeting cellular oncoproteins and enzymes such as BCR-ABL, JAK2, Bruton tyrosine kinase, FLT3, BCL-2, IDH1, IDH2, are biomarker-driven chemotherapy-free agents approved for several major hematological malignancies. LOXO-305, asciminib, "off-the-shelf" universal CAR-T cells and BCMA-directed immunotherapeutics as well as data from clinical trials on many novel agents and regimens were updated at the 2020 American Society of Hematology (ASH) Annual Meeti

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… This combination appeared to be tolerable with cytopenia as predominant adverse events [ 123 ]. CAR-T update A cohort of 19 CLL patients with prior exposure to BTK inhibitor and half also exposed to venetoclax was tested in a phase 1 trial TRANSCEND CLL 004 using liso-cel with ibrutinib [ 124 ]. … Addition of venetoclax caused more cytopenia, which was manageable with shortened course of venetoclax on subsequent cycles upon CRc achieved. Therefore, gilteritinib in combination with venetoclax could be an optimal treatment for Flt3 -mutated rrAML. …

Chimeric Antigen Receptor T-Cell Revolution Remodeling Immunity to Conquer Autoimmune Disease.

Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking technology in tumor immunotherapy, has demonstrated unprecedented potential in the field of autoimmune diseases in recent years. This article provides a systematic review of the developmental trajectory and core concepts of CAR-T-cell therapy in autoimmune diseases, emphasizing its conceptual evolution from traditional "killing" strategies to "precision immune remodeling". Leveraging multitarget approaches (e.g., CD19 and B-cell maturation antigen) and chimeric autoantigen receptor technology, it achieves efficient elimination

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… CD19 CAR-T cells can deplete B cells and CD19-positive plasma cells, leading to secondary hypogammaglobulinemia, whereas immune effector cell-associated hematologic toxicity exacerbates immunodeficiency through cytopenias (anemia, neutropenia, etc.). …

Pharmacological Strategies for Mitigating Cytarabine-Induced Multi-Organ Toxicity: A Scoping Review on Mechanisms, Efficacy and Clinical Implications.

BACKGROUND: Cytarabine (Ara-C) remains the cornerstone of remission-induction and consolidation chemotherapy for acute myeloid leukemia (AML) and related hematological malignancies. Despite more than six decades of clinical use, its multi-organ toxicity continues to be managed almost exclusively through dose attenuation and supportive care, with no approved upstream pharmacological prevention strategy available. OBJECTIVES: This scoping review aimed to systematically map the breadth and nature of pharmacological agents tested in vivo for their capacity to mitigate cytarabine-induced multi-org

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… Ara-C-induced injury to both HSPCs and the sinusoidal endothelium disrupts this architecture, contributing to prolonged cytopenias that extend well beyond the direct cytotoxic phase. …

Plasma cell targeting with the anti-CD38 antibody daratumumab in myalgic encephalomyelitis/chronic fatigue syndrome-a clinical pilot study.

BackgroundMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) entails low quality of life for patients and massive societal costs. There is an urgent need for elucidation of disease mechanisms and for rational treatment. Our working hypothesis is that ME/CFS in a subgroup of patients is associated with functional autoantibodies emerging after an infection, and that plasma-cell depletion with transient reductions in serum immunoglobulins will have a beneficial effect on patients' symptoms.ObjectiveTo evaluate feasibility and toxicity of plasma-cell targeting treatment using the subcutan

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… In autoimmune haemolytic anaemia ( 53 ), anti-phospholipid syndrome ( 54 ), treatment-refractory autoimmune cytopenias, cold agglutinin disease, and other autoimmune diseases (ITP, systemic lupus, anti-CASPR2 encephalitis, rheumatoid arthritis, ANCA-associated vasculitis) daratumumab has shown high efficacy …

Drug-Induced Periocular and Ocular Surface Disorders: An EAACI Position Paper.

Various systemic and topical medications can induce ocular and periocular cutaneous adverse effects (AEs), ranging from mild to severe. These AEs may lead to ocular surface (OS) damage and, in some cases, life-threatening complications. Drug-induced ocular adverse reactions are generally classified into two primary categories: toxic reactions and/or allergic hypersensitivity reactions, which can be IgE or non-IgE-mediated. Systemic antibiotics, antivirals, and anticonvulsants can trigger adverse reactions that may involve the OS. Drugs like antihistamines, beta-blockers, antipsychotics, antide

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… These include infections (reactivation of latent tuberculosis), lymphomas, congestive heart failure, cytopenia, demyelinating disorders, lupus‐like syndromes, and induction of autoantibodies. Anterior uveitis has been identified as the most common ocular AE. …

Are we there yet? CAR-T therapy in multiple myeloma.

The last few years have seen a revolution in cellular immunotherapies for multiple myeloma (MM) with novel antigen targets. The principle new target is B-cell maturation antigen (BCMA). Autologous chimeric antigen receptor T-cell (CAR-T) therapy directed against BCMA was first approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2021, although approval by the National Institute for Health and Care Excellent (NICE) is awaited. Initial response rates in patients with heavily pretreated MM have been impressive, but patients are still relapsing. Furthermore,

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… Comprehensive characterization of prolonged unexplained cytopenias in relapsed/refractory multiple myeloma patients following BCMA‐directed CAR‐T cell therapy . …

" Нанотехнология " : новые стратегии для многократной терапии миеломы.

Достижения в области нанотехнологии открыли новые возможности для диагностики и лечения множественной миеломы (ММ), гематологической злокачественности, характеризующейся клональным распространением плазменных клеток в костном мозге. В этом обзоре раскрывается потенциал нанотехнологии для революции миэломы с уделением особого внимания системам доставки наркотиков наночастиц, методам наномасштабной съемки и наноиммунотерапии. Системы доставки наркотиков, основанные на нанопартии, обеспечивают повышенную целенаправленность наркотиков, снижение системной токсичности и повышение терапевтической эфф

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… introduce further unique side effects by engaging the immune system against myeloma cells, leading to cytokine release syndrome (CRS), neurotoxicity or ICANS (also known as immune effector cell-associated neurotoxicity syndrome), hematologic complications, and heightened infection risks due to prolonged cytopenias …