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From Molecular Precision to Clinical Practice: A Comprehensive Review of Bispecific and Trispecific Antibodies in Hematologic Malignancies.

Multispecific antibodies have redefined the immunotherapeutic landscape in hematologic malignancies. Bispecific antibodies (BsAbs), which redirect cytotoxic T cells toward malignant targets via dual antigen engagement, are now established components of treatment for diseases such as acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and multiple myeloma (MM). Clinical trials of agents like blinatumomab, glofitamab, mosunetuzumab, and teclistamab have demonstrated deep and durable responses in heavily pretreated populations. Trispecific antibodi

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… Retreatment and Approaches to Overcome Resistance Efforts to overcome resistance after failure of bispecific or trispecific antibody therapy have focused on multiple complementary strategies. …

Cancer Immunotherapy Beyond Checkpoint Blockade: JACC: CardioOncology State-of-the-Art Review.

Avoidance of immune destruction is recognized as one of the hallmarks of cancer development. Although first predicted as a potential antitumor treatment modality more than 50 years ago, the widespread clinical use of cancer immunotherapies has only recently become a reality. Cancer immunotherapy works by reactivation of a stalled pre-existing immune response or by eliciting a de novo immune response, and its toolkit comprises antibodies, vaccines, cytokines, and cell-based therapies. The treatment paradigm in some malignancies has completely changed over the past 10 to 15 years. Massive effort

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… Long-term outcomes and responses to retreatment in patients with melanoma treated with PD-1 blockade J Clin Oncol 38 2020 1655 1663 32053428 10.1200/JCO.19.01464 PMC7238490 129 Mok T.S.K. Wu Y.L. Kudaba I. …

Engineering enhanced CAR T-cells for improved cancer therapy.

Chimeric antigen receptor (CAR) T-cell therapies have evolved from a research tool to a paradigm-shifting therapy with impressive responses in B cell malignancies. This review summarizes the current state of the CAR T-cell field, focusing on CD19- and B cell maturation antigen-directed CAR T-cells, the most developed of the CAR T-cell therapies. We discuss the many challenges to CAR-T therapeutic success and innovations in CAR design and T-cell engineering aimed at extending this therapeutic platform beyond hematologic malignancies.

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… The reinfusion of relapsing leukemia patients with a murine scFv-based CAR has been associated with reduced expansion compared with first infusion 62 , 30 , 31 , suggesting that an immune-mediated mechanism may underlie resistance to retreatment. …

Role of Stem Cell Transplantation in Multiple Myeloma.

Autologous stem cell transplantation (auto-SCT) has been the standard of care in eligible newly diagnosed multiple myeloma (MM) patients. Outcomes of patients with MM have improved significantly due to the advent of several novel drugs. Upfront use of these drugs in induction therapy has significantly increased the rate and depth of responses that have translated into longer remission and survival. This has now raised a debate regarding the role and relevance of auto-SCT in the management of myeloma. However, clinical trials have confirmed the utility of auto-SCT even in the era of novel drugs

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… The options include retreatment with previous regimens, and/or moving on to novel drugs or therapies. However, despite this, patients become resistant to chemotherapy and have progressive MM. Allo-SCT is a reasonable upfront salvage option in these patients and offers a potential cure. …

Approaches and Challenges in the Management of Multiple Myeloma in the Very Old: Future Treatment Prospects.

The increasing incidence of geriatric patients with multiple myeloma has elevated concerns in clinical practice. While the introduction of novel therapeutic agents has substantially improved outcomes in younger patients with myeloma, poorer outcomes remain in older patients. Managing older patients requires a multidisciplinary team approach to consider factors that may influence both treatment selection and outcomes. Aging is associated with remodeling of vital organs, physiological downregulations of basal metabolism, susceptibility to multiple comorbidities with ultimate frailty, thereby con

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… Following relapse after four or more lines, patients can be considered for clinical trials or retreatment with previous agents while providing the best supportive care. …

Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia.

The limited sensitivity of the historical treatment response criteria for acute myeloid leukemia (AML) has resulted in a different paradigm for treatment compared with most other cancers presenting with widely disseminated disease. Initial cytotoxic induction chemotherapy is often able to reduce tumor burden to a level sufficient to meet the current criteria for "complete" remission. Nevertheless, most AML patients ultimately die from their disease, most commonly as clinically evident relapsed AML. Despite a variety of available salvage therapy options, prognosis in patients with relapsed or r

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… Patients who suffer a late relapse, especially one greater than 18 months from initial CR (CR1), can sometimes achieve a second CR (CR2) by retreatment with the same initial induction regimen [ 90 ]. …

Evolving Therapeutic Strategies in ANCA-Associated Vasculitis: Current Standards and Emerging Targets for GPA and MPA.

Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are severe autoimmune disorders characterized by necrotizing small-vessel inflammation, and are classified among anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). Standard induction therapy combines glucocorticoids (GCs) with rituximab (RTX) or cyclophosphamide (CYC), with growing emphasis on GC minimization and selective use of avacopan in patients at high risk of GC toxicity. For maintenance therapy, fixed-interval RTX generally outperforms conventional oral agents and biomarker-guided re-dosin

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… Arnold J Vital EM Dass S Aslam A Rawstron AC Savic S Emery P Md Yusof MY A Personalized Rituximab Retreatment Approach Based on Clinical and B-Cell Biomarkers in ANCA-Associated Vasculitis Front Immunol 2022 12 803175 10.3389/FIMMU.2021.803175/FULL 35095887 PMC8789753 Arnold J, Vital EM, Dass S, Aslam … A, Rawstron AC, Savic S, Emery P, Md Yusof MY (2022) A Personalized Rituximab Retreatment Approach Based on Clinical and B-Cell Biomarkers in ANCA-Associated Vasculitis. …

Сексуальное здоровье после неврологических расстройств: всеобъемлющий обзор данных о лечении.

Предыстория/задачи: Сексуальная дисфункция (СД) и более широкие проблемы сексуального здоровья являются распространенными после неврологических расстройств, однако улики вмешательства разрознены по различным условиям и результатам. В ходе этого зонтичного обзора были собраны и оценены на систематической основе данные о мерах, направленных на УР и сексуальное здоровье неврологических групп населения, а также квалифицированные выводы с использованием достоверной информации. Методы: с момента создания были проведены обыски PubMed, Web of Science, Cochrane Bibrary, Embase, PsycINFO, EBCOCOhost и S

Ex Vivo Treatment Response Prediction in Multiple Myeloma: Assay Formats, Clinical Correlation, and Future Directions.

Ex vivo functional testing for multiple myeloma is rapidly evolving, yet no single assay has reached the level of reliability and clinical utility needed for routine decision-making. Existing approaches generally fall into three categories: 2D cultures, 3D models, and dynamic systems. Each contributes valuable but incomplete insight into therapeutic response. Among these, 2D assays remain the most mature, with the most extensive clinical correlations to date, though their simplified architecture limits their ability to reflect the full complexity of the bone marrow microenvironment. However, 3

T-cell engagers in cancer immunotherapy: mechanisms, challenges, and future perspectives.

T-cell engagers (TCEs) are a rapidly evolving class of cancer immunotherapies that redirect cytotoxic T cells to tumor-associated antigens independently of MHC presentation. This review outlines the development, structural formats, and therapeutic potential of various TCE platforms, including bispecific (BiTEs) and trispecific T-cell engagers (TriTEs), dual affinity re-targeting (DART), and other emerging formats. We also highlight the clinical success in treating hematologic malignancies as demonstrated by agents such as blinatumomab and teclistamab. We also discussed the ongoing challenges i

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… The first scFv domain can be modified to target a wide range of surface antigens, allowing for off-the-shelf therapies that can be used immediately for retreatment. The second scFv binding domain is universally specific for CD3. …

Changing lanes: extending CAR T-cell therapy to high-risk plasma cell dyscrasias.

Chimeric antigen receptor (CAR) cellular therapies have advanced outcomes in challenging hematologic malignancies like leukemia, lymphoma, and multiple myeloma. Plasma cell-directed CAR T-cell therapies have been particularly beneficial in multiple myeloma, suggesting that these agents may have a role in other challenging plasma cell disorders such as systemic AL amyloidosis and plasma cell leukemia. AL amyloidosis is a monoclonal plasma cell disorder resulting in the deposition of protein fibrils that compromise end-organ function. Delays in diagnosis can result in end-organ dysfunction and o

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… Retreatment with the initial therapy is reasonable, particularly if relapse-free for over 2 years ( 39 , 79 ). Salvage ASCT is also an option for young, eligible, transplant-naïve patients ( 39 ). Venetoclax should be considered for patients with t(11;14) ( 69 ). …

Novel therapeutic strategies targeting resistance mechanisms in hematologic malignancies: from BCL2 inhibition to immunomodulatory approaches.

BACKGROUND: Hematologic malignancies, including chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM), are characterized by high relapse rates due to intrinsic and acquired drug resistance. Resistance mechanisms often involve dysregulation of apoptosis pathways, such as B-cell lymphoma 2 (BCL2) family overexpression, and immune evasion through microenvironment modulation. PURPOSE: This review synthesizes recent advances (2020-2025) in therapeutic strategies targeting these mechanisms, focusing on BCL2 inhibition and immunomodul

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… The MURANO study: final analysis and retreatment/crossover substudy results of VenR for patients with relapsed/refractory CLL. Blood 145 (23), 2733–2745. 10.1182/blood.2024025525 Kelly P. N., Strasser A. (2011). The role of Bcl-2 and its pro-survival relatives in tumourigenesis and cancer therapy. …

The Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of acute leukemia.

Acute leukemia is a constellation of rapidly progressing diseases that affect a wide range of patients regardless of age or gender. Traditional treatment options for patients with acute leukemia include chemotherapy and hematopoietic cell transplantation. The advent of cancer immunotherapy has had a significant impact on acute leukemia treatment. Novel immunotherapeutic agents including antibody-drug conjugates, bispecific T cell engagers, and chimeric antigen receptor T cell therapies have efficacy and have recently been approved by the US Food and Drug Administration (FDA) for the treatment

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… therapies including BiTEs and CAR T cells makes decisions on optimal treatment sequencing challenging, especially given the possibility for relapse mediated by antigen loss. 95 Options for patients who relapse post-CAR T cell therapy include salvage chemotherapy, clinical trial enrollment, allo-HCT, or retreatment …

Complication from Desensitization

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… Thus, retreatment after this period may be possible and requires further investigation. …

Application and Challenges of Chimeric Antigen Receptor T Cell Therapy in Systemic Rheumatic Diseases and Autoimmune Disorders.

Chimeric antigen receptor T (CAR-T) cell therapy, originally developed for hematologic malignancies, has emerged as a transformative candidate for systemic rheumatic diseases and autoimmune disorders (AIDs). Its unique efficacy in refractory AIDs relies on depleting autoreactive B cells and driving antigen-naïve immune reconstitution, achieving durable drug-free remission in early-phase trials. Despite promising clinical and serological responses lasting 2-5 years without long-term immunosuppression, the field faces unmet needs: complex manufacturing, limited tissue penetration, antigen escape

Relapsed/Refractory Multiple Myeloma: A Review of Available Therapies and Clinical Scenarios Encountered in Myeloma Relapse.

Multiple myeloma remains an incurable disease with the usual disease course requiring induction therapy, autologous stem cell transplantation for eligible patients, and long-term maintenance. Risk stratification tools and cytogenetic alterations help inform individualized therapeutic choices for patients in hopes of achieving long-term remissions with preserved quality of life. Unfortunately, relapses occur at different stages of the course of the disease owing to the biological heterogeneity of the disease. Addressing relapse can be complex and challenging as there are both therapy- and patie

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… Retreatment with DARA in combination with IMiDs specifically has been shown to overcome refractoriness to either agent in the frontline setting. …

Antibody-based drug delivery systems for cancer therapy: Mechanisms, challenges, and prospects.

In recent years, antibody-based cancer therapy has emerged as one of the efficient therapeutic strategies, such as immune checkpoint inhibitors (ICIs), angiogenesis inhibitors, antibody-drug conjugates (ADCs), multi-specific antibodies, and chimeric antigen receptor T (CAR-T) cells, among others. To date, various drug delivery platforms have been developed to improve the bioavailability, delivery convenience, and reduced toxicity towards increased therapeutic efficacy of antibodies. Herein, we emphasize the clinical manifestations of various antibody-based tumor therapies, highlighting their m

Beneath the surface in autoimmune hemolytic anemia: pathogenetic networks, therapeutic advancements and open questions.

In recent years, the pathophysiologic framework of autoimmune hemolytic anemias (AIHAs) has evolved considerably, extending beyond the simplistic paradigm of antibody-mediated red blood cell (RBC) destruction, which is now recognized as a downstream consequence of a broader immune dysregulation. AIHA is fundamentally orchestrated by a complex interplay between innate and adaptive immune components, including autoreactive B and T lymphocytes, macrophages, and the reticuloendothelial system. Central to disease pathogenesis are two interrelated mechanisms: clonal B-cell expansion with autoantibod

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… Nonetheless, responses are often transient, and the efficacy of retreatment remains unclear. …

Potential role of immunotherapy and targeted therapy in the treatment of cancer: A contemporary nursing practice.

Immunotherapy and targeted therapy have emerged as promising therapeutic options for cancer patients. Immunotherapies induce a host immune response that mediates long-lived tumor destruction, while targeted therapies suppress molecular mechanisms that are important for tumor maintenance and growth. In addition, cytotoxic agents and targeted therapies regulate immune responses, which increases the chances that these therapeutic approaches may be efficiently combined with immunotherapy to ameliorate clinical outcomes. Various studies have suggested that combinations of therapies that target diff

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… Velcade (bortezomib) receives 2 new FDA indications: for retreatment of patients with multiple myeloma and for first-line treatment of patients with mantle-cell lymphoma. Am Health Drug Benefits. 2015;8:135. 103. Robak P., Robak T. …

Bridging the Gap in Understanding Bone Metastasis: A Multifaceted Perspective.

The treatment of patients with advanced cancer poses clinical problems due to the complications that arise as the disease progresses. Bone metastases are a common problem that cancer patients may face, and currently, there are no effective drugs to treat these individuals. Prostate, breast, and lung cancers often spread to the bone, causing significant and disabling health conditions. The bone is a highly active and dynamic tissue and is considered a favorable environment for the growth of cancer. The role of osteoblasts and osteoclasts in the process of bone remodeling and the way in which th

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… Additionally, the feasibility of retreatment with RPs and their integration with standard chemotherapy regimens are subjects of ongoing investigation. …