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Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.

BACKGROUND: CAR-T cell therapy represents a major breakthrough in hematological malignancies. However, the trade-off between insufficient treatment persistence and treatment-related toxicities (especially cytokine release syndrome, CRS) still limits its wider clinical application. MAIN BODY: Our review aims to reframe the understanding of this central dilemma. It posits that the dynamic imbalance of intracellular signaling networks and external inflammation in the tumor microenvironment (TME) are the causes of insufficient persistence of CAR-T cells and the severe CRS. The intracellular signa

Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab.

CD38 is a transmembrane glycoprotein with ectoenzymatic activity involved in regulation of migration, signal transduction, and receptor-mediated adhesion. CD38 is highly expressed on various malignant cells, including multiple myeloma (MM), and at relatively low levels in other tissues, making it a suitable target for therapeutic antibodies. Several anti-CD38 therapies have been, or are being, developed for the treatment of MM, including daratumumab and isatuximab (SAR650984), respectively. Studies have shown that anti-CD38 therapies are effective in the treatment of relapsed/refractory MM and

Antibodies to watch in 2021.

In this 12th annual installment of the Antibodies to Watch article series, we discuss key events in antibody therapeutics development that occurred in 2020 and forecast events that might occur in 2021. The coronavirus disease 2019 (COVID-19) pandemic posed an array of challenges and opportunities to the healthcare system in 2020, and it will continue to do so in 2021. Remarkably, by late November 2020, two anti-SARS-CoV antibody products, bamlanivimab and the casirivimab and imdevimab cocktail, were authorized for emergency use by the US Food and Drug Administration (FDA) and the repurposed an

The 45th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians - Oral Session.

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Perspective recommendations on geriatric support for older adults with multiple myeloma based on challenges faced by a multidisciplinary team.

BACKGROUND: Multiple Myeloma (MM) predominantly affects older adults, with a median diagnosis age of 70 years, posing challenges in management due to frailty, comorbidities, and age-related physiological changes. As the aging population grows, the prevalence of MM in older patients is expected to rise, requiring improved clinical strategies. METHODS: This consensus report outlines a multidisciplinary framework for the identification, geriatric assessment (GA), and management of older adults with MM, emphasizing the role of frailty assessments, such as the IMWG frailty score, in tailoring trea

Infections associated with immunotherapeutic and molecular targeted agents in hematology and oncology. A position paper by the European Conference on Infections in Leukemia (ECIL).

A multitude of new agents for the treatment of hematologic malignancies has been introduced over the past decade. Hematologists, infectious disease specialists, stem cell transplant experts, pulmonologists and radiologists have met within the framework of the European Conference on Infections in Leukemia (ECIL) to provide a critical state-of-the-art on infectious complications associated with immunotherapeutic and molecular targeted agents used in clinical routine. For brentuximab vedotin, blinatumomab, CTLA4- and PD-1/PD-L1-inhibitors as well as for ibrutinib, idelalisib, HDAC inhibitors, mTO

Cost-Effectiveness of Elranatamab Versus Teclistamab for the Management of Patients with Triple-Class Exposed Relapsed/Refractory Multiple Myeloma in Italy.

BACKGROUND: Multiple myeloma remains an incurable malignancy in which patients ultimately experience relapses and refractory disease despite therapeutic advances. Triple-class exposed relapsed/refractory MM (TCE/RRMM) patients represent both a population with high unmet clinical needs and a substantial economic burden for the Italian National Health Service (NHS). Recently, BCMA-CD3 bispecific antibodies, including elranatamab and teclistamab, have expanded the treatment options for these patients. This study aimed to evaluate the cost-effectiveness of elranatamab versus teclistamab in adults

How First-Line Therapy is Changing in Transplant-Eligible Multiple Myeloma Patients.

Multiple myeloma is a malignant haematological neoplasm characterised by the proliferation of plasma cells in the bone marrow. Each year, over 35,000 new cases are diagnosed in the United States, and nearly 13,000 patients die from the disease.1 The main cause of morbidity is bone disease, characterised by osteolytic lesions, which, unlike other malignancies that metastasise to bone, are not followed by new bone formation.2 Other major clinical manifestations include anaemia, hypercalcemia, renal failure, and an increased risk of infections. Approximately 1-2% of patients present with extramed

Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response.

Cancers are highly complex diseases that are characterized by not only the overgrowth of malignant cells but also an altered immune response. The inhibition and reprogramming of the immune system play critical roles in tumor initiation and progression. Immunotherapy aims to reactivate antitumor immune cells and overcome the immune escape mechanisms of tumors. Represented by immune checkpoint blockade and adoptive cell transfer, tumor immunotherapy has seen tremendous success in the clinic, with the capability to induce long-term regression of some tumors that are refractory to all other treatm

Baseline immunonutritional status drives CAR T-cell efficacy, survival, and safety in R/R lymphoma: validation of a pre-lymphodepletion PNI threshold.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape for relapsed/refractory (R/R) lymphoma. However, heterogeneous responses and treatment-related toxicities remain significant challenges. The prognostic nutritional index (PNI), reflecting both nutritional status and systemic immune competence, has emerged as a potential biomarker in various malignancies. This study aimed to evaluate the predictive value of the PNI assessed specifically prior to lymphodepletion in patients with R/R lymphoma receiving CAR T-cell therapy. We retrospectively analyzed 449 pati

A Journey through the Inter-Cellular Interactions in the Bone Marrow in Multiple Myeloma: Implications for the Next Generation of Treatments.

Tumors are composed of a plethora of extracellular matrix, tumor and non-tumor cells that form a tumor microenvironment (TME) that nurtures the tumor cells and creates a favorable environment where tumor cells grow and proliferate. In multiple myeloma (MM), the TME is the bone marrow (BM). Non-tumor cells can belong either to the non-hematological compartment that secretes soluble mediators to create a favorable environment for MM cells to grow, or to the immune cell compartment that perform an anti-MM activity in healthy conditions. Indeed, marrow-infiltrating lymphocytes (MILs) are associate

Воздействие высокоэффективной терапии множественного склероза на клетки B.

Множественный склероз (MS) представляет собой хроническое воспалительное и нейродегенеративное аутоиммунное расстройство центральной нервной системы, характеризующееся демиэлированием и нейродегенерацией. Традиционно рассматриваемая как болезнь с Т-клетоклетками, ключевая роль В-лимфоцитов в его патогенезе через различные механизмы, способствующие воспалению и автоматической активности, получает все большее признание. Риск долгосрочной инвалидности у пациентов с НР может быть снижен за счет раннего начала лечения, в частности с помощью высокоэффективной терапии. Цель этого обзора состоит в том

Cellular based treatment modalities for unresectable hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is unfortunately associated with an overall poor prognosis and high mortality. Early and intermediate stages of HCC allow for treatment with surgical resection, ablation and even liver transplantation, however disease progression warrants conventional systemic therapy. For years treatment options were limited to molecular-targeting medications, of which sorafenib remains the standard of care. The recent development and success of immune checkpoint inhibitors has proven to be a breakthrough in the treatment of

Immune Checkpoint Inhibitors and Immunomodulators for Cancer Immunotherapy: Insights Into Resistance and Therapeutic Strategies.

Cancer immunotherapy has redefined cancer treatment. However, the molecular and cellular basis of immune evasion and therapeutic resistance remains incompletely understood. Early immune checkpoint inhibitors have delivered significant clinical benefit, but their efficacy and durability remain limited in many patients. These limitations have driven the exploration of next-generation immune checkpoints and additional regulatory pathways that shape tumor-immune interactions. Recent advances have broadened the immune checkpoint landscape and revealed new targets. These targets operate within inter

Mechanisms of Cancer Resistance to Immunotherapy.

Over the last decade, based on the extensive development of preclinical animal studies and clinical trials, the efficacy, and mechanisms of immunotherapy have been fully explored. Significant and lasting clinical responses with immunotherapy provide a new breakthrough treatment for a variety of refractory cancer histologies, which gradually change the treatment pattern of tumors. However, although immune checkpoint inhibitor drugs are promising for achieving longer-term efficacy, their benefits in the overall population are still very low, such as low frequency of response in some common tumor

CNS Вовлечение нескольких серий дел Myeloma-A и наррутический литературный обзор.

Фон: участие центральной нервной системы (ЦНС) в множественной миеломе (ММ) представляет собой экстрамуллярное проявление заболевания, которое часто является весьма сложным для врачей, поскольку неврологические симптомы могут легко перекликаться с симптомами, связанными с гиперкалкемией, уремией, высокой вязкостью крови или связанной с лечением нейропатией. Цели: Это ретроспективное исследование было проведено в Клиническом институте Фундэни в Бухаресте с целью выявления и систематического анализа ряда клинических случаев, диагностированных внематочным заболеванием. Методы: В период с 2019 по

HMGB1: новая биомаркировка и лечебная цель аутоиммунной и аутовоспалительной кожных заболеваний.

Вставка 1 группы высокой подвижности (HMGB1) выражена почти во всех человеческих клетках. Во время активации клеток и клеточной смерти нуклеопротеин HMGB1 может перемещаться в внеклеточное пространство, тем самым посредничая ранним подстрекательским ответом как сигнализация или молекулярный рисунок, связанный с повреждением (DAMP). Внешнеклеточный HMGB1 взаимодействует с иммунными клетками, связываясь с системой распознавания рецепторов Toll-подобных (TLR), включая TLR2 и TLR4, и рецептором для современных продуктов для гликации (RAGE), тем самым содействуя иммунной реакции для защиты хоста от

Chimeric antigen receptor T cell therapy: a new emerging landscape in autoimmune rheumatic diseases.

Chimeric antigen receptor T cell (CAR-T) therapy, an innovative immune cell therapy, has revolutionized the treatment landscape of haematological malignancies. The past 2 years has witnessed the successful application of CD19-targeting CAR constructs in refractory cases of autoimmune rheumatic diseases, including systemic lupus erythematosus, systemic sclerosis and anti-synthetase syndrome. In comparison with existing B cell depletion therapies, targeting CD19 has demonstrated a more rapid and profound therapeutic effect, enabling drug-free remission with manageable adverse events. These promi

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… The first generation of CARs consisted of a single-chain variable fragment (scFv) derived from an antibody as the extracellular antigen-binding domain, a hinge or spacer, a transmembrane domain, and an intracellular signalling domain, CD3ζ, from a TCR–CD3 complex [ 3 ] ( Fig. 2 ). …

Paediatric intestinal pseudo-obstruction: a scoping review.

Paediatric intestinal pseudo-obstruction (PIPO) encompasses a group of rare disorders in which patients present with the clinical features of bowel obstruction in the absence of mechanical occlusion. The management of PIPO presents a challenge as evidence remains limited on available medical and surgical therapy. Parenteral nutrition is often the mainstay of therapy. Long-term therapy may culminate in life-threatening complications including intestinal failure-related liver disease, central line thrombosis and sepsis. Intestinal transplantation remains the only definitive cure in PIPO but is a

Clonal evolution and apoptosis resistance in myelodysplastic neoplasms and acute myeloid leukemia under treatment: insights from integrative longitudinal profiling.

Treatment of high-risk Myelodysplastic Neoplasms (hr-MDS) and (secondary) Acute Myeloid Leukemia (AML) remains a clinical challenge. The combination of azacitidine and venetoclax (aza/ven) may improve treatment outcomes, but still fails in a significant fraction of patients. We established a single-center collection of longitudinal samples from patients with MDS and AML/sAML and performed comprehensive genetic, proteomic and functional apoptosis profiling to identify biomarkers and targetable escape mechanisms to aza/ven. Baseline genetic characterization (n = 55) identified high-risk genetic