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Prevalence of symptomatic toxicities for novel therapies in adult oncology trials: a scoping review.

BackgroundPatients' self-report of their symptoms can provide important data for the evaluation of treatment benefit and tolerability of oncology drugs. Contemporary treatment approaches, including immunotherapy and molecular targeted therapies, have unique toxicities based on their novel mechanisms of action. This scoping review aimed to summarize evidence from existing reviews and clinical practice guidelines to examine the type and prevalence of toxicities including symptomatic adverse events (sympAEs) for adult cancer patients to inform clinical care and therapeutic trials.MethodsA systema

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… toxicity (34%) Misc: injection site reaction, CRS (35%-100%) Kennedy (2020) | Review of trials data and ASTCT Consensus Guidelines | Hematological (B lymphoid malignancies) | Anti-CD19 CAR-T cells | Skin: rash Pain: myalgias Sleep/Wake: fatigue Misc: fever | GI: hepatic dysfunction, hepatosplenomegaly, hyperferritinemia …

Tissue-Resident Myeloid and Histiocytic Cells in Health and Disease: Novel Emerging Concepts.

Although all myeloid cells are considered to derive from hematopoietic stem cells, the cells in each myeloid lineage are heterogeneous populations, and their distribution and functions vary, depending on underlying physiologic and pathologic processes, age, sex, and genetic and epigenetic signatures. In general, myeloid cells can be separated into circulating and tissue-resident cells. Tissue-resident myeloid cells can further be divided into cells derived from circulating monocytes, circulating stem cells, or local tissue-restricted stem or progenitor cells. Depending on underlying diseases a

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… These criteria include (i) fever, (ii) splenomegaly, (iii) marked cytopenia in at least two cell lineages, (iv) hypertriglyceridemia (> 265 mg/dL) or hypofibrinogenemia (< 150 mg/dL), (v) hyperferritinemia (>500 ng/mL; in most cases much higher levels are found), vi.) elevated serum levels of soluble …

Toxicity management strategies for next-generation novel therapeutics in multiple myeloma.

The therapeutic options available for patients with multiple myeloma have greatly expanded over the past decade and incorporating these novel agents into routine clinical practice has significantly improved outcomes. The next generation of therapeutics is available for relapsed and refractory patients either as standard of care or in clinical trial, and these drugs represent a generational paradigm shift. Patients now have access to a multitude of novel immunotherapeutics, including monoclonal antibodies, an antibody-drug conjugate, chimeric antigen receptor T-cells (CAR-T), and bispecific T-c

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… HLH, also known as macrophage-activation syndrome (MAS), is another complication of CAR-T therapy and was present in 4–8% of patients in the Ide-cel dataset. 69 This entity is difficult to distinguish from CRS as both present with high fevers, organ toxicity, cytopenias, hyperferritinemia, and high levels …

The CoV-2 outbreak: how hematologists could help to fight Covid-19.

COVID-19 is a medical emergency, with 20 % of patients presenting with severe clinical manifestations. From the pathogenetic point of view, COVID-19 mimics two other well-known diseases characterized by cytokine storm and hyper-activation of the immune response, with consequent organ damage: acute graft-versus-host disease (aGVHD) and macrophage activation syndrome (MAS). Hematologists are confident with these situations requiring a prompt therapeutic approach for switching off the uncontrolled cytokine release; here, we discuss pros and cons of drugs that are already employed in hematology in

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… From the diagnostic point of view, MAS is a febrile condition characterized by hyperferritinemia, multilineage cytopenia, coagulopathy, transaminitis, high levels of triglycerides, hypofibrinogenemia and splenomegaly. …

The Challenging Approach to Multiple Myeloma: From Disease Diagnosis and Monitoring to Complications Management.

The outcome of multiple myeloma (MM) has significantly improved in the last few decades due to several factors such as new biological discoveries allowing to better stratify disease risk, development of more effective therapies and better management of side effects related to them. However, handling all these aspects requires an interdisciplinary approach involving multiple knowledge and collaboration of different specialists. The hematologist, faced with a patient with MM, must not only choose a treatment according to patient and disease characteristics but must also know when therapy needs t

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… It is characterized as a hyperinflammatory syndrome with macrophage activation and HLH, cytopenia, hyperferritinemia, coagulopathy, hypofibrinogenemia and/or transaminitis [ 104 ]. Prior to infection, a longer CRS duration, grade ≥2 CRS and neurotoxicity were identified as risk factors [ 105 ]. …

CAR T-cells in hematologic malignancies: Advances, challenges, and future directions.

Chimeric antigen receptor (CAR) T-cell therapy has transformed the management of hematologic malignancies, achieving high remission rates in relapsed or refractory B-cell acute lymphoblastic leukemia, large B-cell lymphoma, and multiple myeloma. By redirecting autologous or allogeneic T lymphocytes against tumor-associated antigens such as CD19 and TNFRSF17, CAR T-cells overcome resistance to conventional therapies. Progressive optimization of CAR design-from early constructs to armored and logic-gated platforms-has enhanced persistence, specificity, and safety. Pivotal trials and real-world e

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… It is characterized by extreme hyperferritinemia, cytopenias, organ dysfunction, and uncontrolled macrophage activation, often overlapping clinically with severe CRS. …

Experimental Drugs for Chemotherapy- and Cancer-Related Anemia.

Anemia in cancer patients is a relevant condition complicating the course of the neoplastic disease. Overall, we distinguish the anemia which arises under chemotherapy as pure adverse event of the toxic effects of the drugs used, and the anemia induced by the tumour-associated inflammation, oxidative stress, and systemic metabolic changes, which can be worsened by the concomitant anticancer treatments. This more properly cancer-related anemia depends on several overlapping mechanism, including impaired erythropoiesis and functional iron deficiency, which make its treatment more difficult. Stan

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… Effect of intravenous ascorbic acid in hemodialysis patients with EPO-hyporesponsive anemia and hyperferritinemia. Am J Kidney Dis . 2006;47(4):644–654. doi: 10.1053/j.ajkd.2005.12.025 161. Barni S, Gascòn P, Petrelli F, et al. …

T-клеток, перенаправляющих терапию на рецидив миеломы.

В последние годы использование иммуномодуляционных препаратов, протеиозных ингибиторов и CD38, направленных против моноклонных антител, привело к значительному улучшению общих результатов пациентов с множественной миеломой. Несмотря на эти достижения, рецидивы остаются обычным явлением, и до недавнего времени прогнозы таких пациентов охранялись. Одобрение T-клеток химерика антигенного рецептора (CAR) и Т-комплексов (TCE) значительно повысило выживаемость этих пациентов с тройной и пента-классовой рефракторной болезнью. В настоящем документе рассматриваются клинические результаты, связанные с э

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… IEC-HS is typically associated with the progression or new onset of cytopenias, hyperferritinemia, coagulopathy with hypofibrinogenemia, and/or transaminitis. …

TAM-ing the CIA-Tumor-Associated Macrophages and Their Potential Role in Unintended Side Effects of Therapeutics for Cancer-Induced Anemia.

Cancer-induced anemia (CIA) is a common consequence of neoplasia and has a multifactorial pathophysiology. The immune response and tumor treatment, both intended to primarily target malignant cells, also affect erythropoiesis in the bone marrow. In parallel, immune activation inevitably induces the iron-regulatory hormone hepcidin to direct iron fluxes away from erythroid progenitors and into compartments of the mononuclear phagocyte system. Moreover, many inflammatory mediators inhibit the synthesis of erythropoietin, which is essential for stimulation and differentiation of erythroid progeni

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… Vice versa , increased serum iron (hyperferritinemia) can indicate either parenchymal iron overload or immune activation with subsequent uptake and storage of iron in macrophages. …

Precision immunotherapy with CAR-T cells in pediatric B-cell acute lymphoblastic leukemia: advances and unanswered challenges.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a groundbreaking treatment for pediatric B-cell acute lymphoblastic leukemia (B-ALL), especially for patients with relapsed or refractory disease. CD19-targeted CAR T cells, such as tisagenlecleucel, have demonstrated high rates of complete remission and long-lasting responses in clinical trials. However, challenges such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), antigen escape, and T-cell exhaustion hinder its broader clinical application. Recent advances aim to overcome thes

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… It is characterized by sustained fever, cytopenias, hepatosplenomegaly, hyperferritinemia, coagulopathy, and hemophagocytosis ( 124 ). …

Advances in the clinical application of bispecific antibodies in cancer therapy.

Cancer immunotherapy has emerged as one of the most groundbreaking advancements. However, the tumor microenvironment (TME) is often dominated by various immunosuppressive factors, compromising the efficacy of single-target therapies, leading to non-responsiveness or resistance. Bispecific antibodies (BsAbs) represent an innovative immunotherapeutic strategy with enormous potential for improving cancer treatment outcomes. Unlike monoclonal antibodies, BsAbs can concurrently inhibit multiple pro-tumor pathways, target immune checkpoints to mitigate resistance, and bind to two distinct antigens,

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… trials have reported grade 3–4 CRS events, highlighting its significance as a dose-limiting toxicity. 88 CRS manifests as a systemic inflammatory response ranging from flu-like symptoms to life-threatening shock, accompanied by laboratory abnormalities including cytopenia, elevated liver enzymes, and hyperferritinemia …

T-Cell Redirecting Therapies in Multiple Myeloma: Pathogenesis and Management of Toxicities Beyond CRS and ICANS.

The introduction of chimeric antigen receptor T (CAR-T) cell and bispecific antibody (BsAb) therapies has revolutionized multiple myeloma (MM) treatment, offering exceptional efficacy, and culminating in recent regulatory approval. However, these therapies have brought unique toxicity challenges, manifesting not only with the well-established cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), but also with the emergence of other common and equally distinctive toxicities, including cytopenias, hypogammaglobulinemia, infections, and the rare but l

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… In 2023, however, the ASTCT proposed some consensus criteria for its identification: hyperferritinemia (defined as at least twice the baseline and/or rapidly rising) is required, while the most common manifestations to be considered are cytopenias, decreased fibrinogen, increased transaminases and hemophagocytosis …

Selected Abstracts from the 12th Annual Meeting of the Clinical Immunology Society: 2021 Virtual Annual Meeting: Immune Deficiency and Dysregulation North American Conference.

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Advancing Immunotherapy in Chronic Lymphocytic Leukemia.

The treatment of chronic lymphocytic leukemia (CLL) has significantly shifted from chemoimmunotherapy to targeted therapies like Bruton's tyrosine kinase and BCL2 inhibitors. Despite these advancements, CLL remains an incurable disease characterized by immune dysregulation, therapeutic resistance, and cumulative toxicities. To overcome these challenges, novel immunotherapeutic strategies are emerging as fundamentally different approaches that target immune-tumor interactions. These innovations include novel monoclonal antibodies, bispecific antibodies that redirect T cell cytotoxicity, chimeri

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… Sixty-four percent of patients developed immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), a hyperinflammatory complication of immune effector cell-based therapies characterized by macrophage activation features such as cytopenias, hyperferritinemia, and coagulopathy …

Precision medicine: The use of tailored therapy in primary immunodeficiencies.

Primary immunodeficiencies (PID) are rare, complex diseases that can be characterised by a spectrum of phenotypes, from increased susceptibility to infections to autoimmunity, allergy, auto-inflammatory diseases and predisposition to malignancy. With the introduction of genetic testing in these patients and wider use of next-Generation sequencing techniques, a higher number of pathogenic genetic variants and conditions have been identified, allowing the development of new, targeted treatments in PID. The concept of precision medicine, that aims to tailor the medical interventions to each patie

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… of the diagnosis for HLH, including the most common clinical manifestations like fever, splenomegaly and laboratory alterations: cytopenias of at least two lineages, hypertriglyceridemia or hypofibrinogenemia, hemophagocytosis in primary and secondary lymphoid organs, low or absent NK cell activity, hyperferritinemia …

Immune Dysfunction in Uremia 2020.

Cardiovascular disease and infections are major causes for the high incidence of morbidity and mortality of patients with chronic kidney disease. Both complications are directly or indirectly associated with disturbed functions or altered apoptotic rates of polymorphonuclear leukocytes, monocytes, lymphocytes, and dendritic cells. Normal responses of immune cells can be reduced, leading to infectious diseases or pre-activated/primed, giving rise to inflammation and subsequently to cardiovascular disease. This review summarizes the impact of kidney dysfunction on the immune system. Renal failur

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… Inflammation increases the hepcidin level, resulting in serum hypoferremia and tissue hyperferritinemia [ 123 ]. In CKD, hepcidin may be considered as a link between inflammation and anemia in CKD [ 124 ]. …

Pharmacovigilance in Cell and Gene Therapy: Evolving Challenges in Risk Management and Long-Term Follow-Up.

Cell and gene therapies, including CAR T-cells, CRISPR-based genome editing, and next-generation viral and non-viral delivery platforms, are transforming treatment paradigms across cancer, rare genetic disorders, immune dysregulation, and neurodegenerative disease. These therapies offer curative potential but also present safety challenges owing to prolonged biological activity, systemic immune engagement, and lasting genomic alterations. This review examines the range of related toxicities, including immune complications, genotoxicity, and organ-specific effects, with attention to atypical pr

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… Key laboratory triggers include hyperferritinemia, elevated soluble IL-2 receptor (sCD25), and high levels of IFN-γ and IL-18, although real-time cytokine assays remain investigational. First-line treatment involves high-dose corticosteroids. …

Ход работы сессии 31st Европейский педиатрический конгресс по педиатрии: часть 2.

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Poster Abstracts

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Предварительная обработка сигнатуры эндокринного недоедания прогнозируют клиническую пользу от PD-1/PD-L1 Блокирование гематологовых магнатов.

Гематологические заболевания создают значительное бремя для здоровья людей во всем мире, а запрограммированная клеточная смертность protein-1 (В тыс.PD-1)/запрограммированный смертельный лиганж клеток 1 (В тыс.PD-L1) ингибиторы, революционизирующие лечение в подтипах, таких, как классическая лимфома Ходжкина (cHL) и первичная медистинальная лимфома В-клеток (PMBCL), достигающая высоких объективных показателей ответов (ORR). Однако эффективность варьируется в широких пределах, при этом успех в множестве миеломы ограничен.< 10% ORR) и лейкемии, подчеркивая необходимость лучшего прогнозирования,

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… In hematologic malignancies, hyperferritinemia is a well-known adverse factor in cHL and DLBCL and likely contributes to the immunosuppressive marrow microenvironment that limits PD-1 blockade efficacy in myeloma or leukemia ( 131 ). …