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Efficacy and safety of isatuximab subcutaneous plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma: results of the Phase 2 study IZALCO.

In the Phase 2 IZALCO study, we evaluated efficacy, patient preference, safety and pharmacokinetics for isatuximab administered SC by an innovative on-body injector (OBI) or manual injection, plus carfilzomib-dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM) patients. In Part 1, isatuximab SC was injected manually (cycles 1-6). In Part 2, patients were randomized to isatuximab SC by manual injection (cycles 1-3) followed by OBI administration (cycles 4-6) or to isatuximab OBI (cycles 1-3) followed by manual injection (cycles 4-6). From cycle 7, all patients could choose either

When Cancer Clots: An Extensive Radiologic Analysis of Cancer-Associated Thromboembolism.

Cancer-associated thrombosis (CAT) is a leading cause of morbidity and mortality in patients with malignancy, yet its imaging manifestations extend far beyond the conventional diagnosis of deep vein thrombosis and pulmonary embolism. This comprehensive review examines the full spectrum of CAT as encountered by radiologists, from routine venous thromboembolism to unusual-site thromboses, arterial thromboembolic events, catheter-related complications, and endovascular management strategies. Patients with cancer face a four- to seven-fold increased risk of venous thromboembolism compared with the

Macroglossia due to Systemic Amyloidosis: Is There a Role for Radiotherapy?

BACKGROUND: Macroglossia due to amyloid depositions can cause cosmetic problems and functional disability, and can lead to life-threatening airway obstruction. Management of macroglossia in systemic amyloidosis is controversial, and the role of surgery is unclear. CASE DESCRIPTION: We present a case of a 66-year-old woman affected by macroglossia due to light chain amyloidosis who presented with eating and breathing difficulties. Because of prior successful results of radiotherapy for localized amyloid disease, our patient was treated with external beam radiation therapy (20 Gy in 10 fraction

Cytokine Release Syndrome in the Immunotherapy of Hematological Malignancies: The Biology behind and Possible Clinical Consequences.

Cytokine release syndrome (CRS) is an acute systemic inflammatory syndrome characterized by fever and multiple organ dysfunction associated with (i) chimeric antigen receptor (CAR)-T cell therapy, (ii) therapeutic antibodies, and (iii) haploidentical allogeneic stem cell transplantation (haplo-allo-HSCT). Severe CRS can be life-threatening in some cases and requires prompt management of those toxicities and is still a great challenge for physicians. The pathophysiology of CRS is still not fully understood, which also applies to the identifications of predictive biomarkers that can forecast the

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… The most important organ involvements are reduced renal function, pulmonary edema, cardiac dysfunction with reduced cardiac output, activation of platelets and the coagulation factor cascade with secondary disseminated intravascular coagulopathy (DIC), and central nervous dysfunction with seizures and …

Inpatient Medicine

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Systemic adverse effects and toxicities associated with immunotherapy: A review.

Immunotherapy is rapidly evolving secondary to the advent of newer immunotherapeutic agents and increasing approval of the current agents by the United States Food and Drug Administration to treat a wide spectrum of cancers. Immunotherapeutic agents have gained immense popularity due to their tumor-specific action. Immunotherapy is slowly transforming into a separate therapeutic entity, and the fifth pillar of management for cancers alongside surgery, radiotherapy, chemotherapy, and targeted therapy. However, like any therapeutic entity it has its own adverse effects. With the increasing use o

Amyloidosis in Childhood: A Review of Clinical Features and Comparison with Adult Forms.

Amyloidosis is a rare multisystem disorder characterized by extracellular accumulation of insoluble fibrils in various organs and tissues. The most common subtype in the pediatric population is systemic reactive amyloidosis, typically developing secondary to chronic inflammatory conditions and resulting in deposition of serum amyloid A protein in association with apolipoprotein HDL3. Clinical presentation is highly variable and is mostly influenced by specific organs involved, precursor protein type, and extent of amyloid deposition, often closely reflecting clinical features of the underlying

Management of Multiple Myeloma: A Review for General Practitioners in Oncology.

Multiple myeloma (MM) is a malignant clonal plasma cell disorder in the bone marrow and is the second-most common hematologic malignancy in adults. Although patients with MM have a moderate life expectancy, it remains a heterogeneous disease that often requires multiple lines of chemotherapy for durable control and long-term survival. This review outlines current management strategies for both transplant-eligible and transplant-ineligible patients as well as for relapsed and refractory disease. Advances in drug therapies have widened management options and improved survival. In this paper, we

Teclistamab Treatment Followed by Heart Transplantation for Advanced Immunoglobulin Light Chain Amyloid Cardiomyopathy.

BackgroundImmunoglobulin light chain (AL) cardiac amyloidosis carries high mortality, particularly when refractory to standard plasma cell-directed therapy. Deep hematologic remission is essential for heart transplant eligibility.Case summaryA 37-year-old woman with advanced AL cardiomyopathy and refractory plasma cell dyscrasia did not respond to daratumumab-based therapy and could not tolerate venetoclax. She developed rapidly progressive, inotrope-dependent heart failure. Salvage therapy with a B-cell maturation antigen-directed bispecific antibody, teclistamab, induced a rapid, minimal res

Hypertension in Cardio-Oncology Clinic: an update on etiology, assessment, and management.

Hypertension is one of the most common comorbidity and the leading cause of cancer-related death in cancer patients. The prevalence of hypertension in cancer patients is much higher than that of the general population. In the older population of cancer patients, specific cancer treatments such as new tyrosine kinase inhibitors and Vascular endothelial growth factor inhibitor drugs give rise to hypertension in cancer patients; The aim of present study is to provide a detailed discussion etiologies of cancer treatment-induced hypertension and explore the most innovative diagnostic and management

Сфингосин 1-phosphate рецептор 1 Модераторы оказывают нейрозащитное воздействие на нарушения центральной нервной системы.

Фингозин 1-phosphate (S1P) Пути подачи сигналов имеют важные и разнообразные функции. Рецепторы S1P (S1PR) участвуют в регулировании торговли лимфоцитами, сердечно-церебральной функции, сосудистой проницаемости и бронхиолярного тона и были признаны в качестве терапевтических целей для различных заболеваний. Ряд лекарственных средств, связанных с траекторией подачи сигналов S1P, был утвержден для клинического использования при лечении множественных склерозов, и многие аналогичные препараты в настоящее время также проходят испытания в ходе клинических испытаний на различных этапах. Как представл

Oral ixazomib, lenalidomide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma.

Continuous lenalidomide-dexamethasone (Rd)-based regimens are among the standards of care in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. The oral proteasome inhibitor ixazomib is suitable for continuous dosing, with predictable, manageable toxicities. In the double-blind, placebo-controlled TOURMALINE-MM2 trial, transplant-ineligible NDMM patients were randomized to ixazomib 4 mg (n = 351) or placebo (n = 354) plus Rd. After 18 cycles, dexamethasone was discontinued and treatment was continued using reduced-dose ixazomib (3 mg) and lenalidomide (10 mg) until progres

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… “Heart failure” included the preferred terms of cardiac failure, pulmonary edema, cardiac failure congestive, cardiomegaly, diastolic dysfunction, orthopnea, acute pulmonary edema, pulmonary congestion, right ventricular failure, left ventricular failure. …

The role of carfilzomib in relapsed/refractory multiple myeloma.

Carfilzomib is the second proteasome inhibitor approved for relapsed multiple myeloma. Since its approval in 2012, carfilzomib has been an active and versatile drug, based on its efficacy as a single agent; superiority as a doublet with dexamethasone compared with bortezomib and dexamethasone; and as a partner in diverse three drug combinations such as with lenalidomide or daratumumab. While it has an established place in relapsed disease, clinicians should be aware of its cardiovascular and renal adverse event profile, which is manageable, in order to optimize outcomes. This review will provi

Complications after CD19+ CAR T-Cell Therapy.

Clinical trials demonstrated that CD19+ chimeric antigen receptor (CAR) T-cells can be highly effective against a number of malignancies. However, the complete risk profile of CAR T-cells could not be defined in the initial trials. Currently, there is emerging evidence derived from post approval studies in CD19+ CAR T-cells demonstrating both short-term and medium-term effects, which were unknown at the time of regulatory approval. Here, we review the incidence and the current management of CD19+ CAR T-cell complications. We highlight frequently occurring events, such as cytokine release syndr

Recognition and management of early complications in CAR-T cell therapy and virus-specific T-lymphocyte therapy: a practical clinical reference.

BACKGROUND: Cellular immunotherapies-including chimeric antigen receptor T-cell (CAR-T) therapies and adoptive transfer of virus-specific T lymphocytes (VSTs) - have transformed the treatment of refractory hematological malignancies and post-transplant infectious complications. Eight products are currently authorized by the European Medicines Agency, encompassing seven autologous CAR-T products targeting CD19 or BCMA and tabelecleucel (Ebvallo), the first approved allogeneic off-the-shelf EBV-specific T-cell product for EBV-positive post-transplant lymphoproliferative disease. Despite their cl

A lost race against time-a rare case of AL amyloidosis.

INTRODUCTION: Amyloidosis is a rare multi-system disease that can affect the heart. Recent advances have been made in finding successful treatments for these patients. Nonetheless, cardiac amyloidosis continues to carry high morbidity and mortality. CASE PRESENTATION: This case refers to a 52-year-old man presenting with signs and symptoms of heart failure. Electrocardiogram showed q waves in V1-V3 and T wave inversion in the inferior and lateral leads. Echocardiography revealed moderate concentric left ventricular hypertrophy, with preserved biventricular systolic function and no other chang

Drug Repurposing for the Management of Depression: Where Do We Stand Currently?

A slow rate of new drug discovery and higher costs of new drug development attracted the attention of scientists and physicians for the repurposing and repositioning of old medications. Experimental studies and off-label use of drugs have helped drive data for further studies of approving these medications. A deeper understanding of the pathogenesis of depression encourages novel discoveries through drug repurposing and drug repositioning to treat depression. In addition to reducing neurotransmitters like epinephrine and serotonin, other mechanisms such as inflammation, insufficient blood supp

45th International Symposium on Intensive Care & Emergency Medicine.

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A 65-Year-Old Woman with an Enlarged Tongue Due to Amyloidosis.

BACKGROUND Amyloidosis is a clinical condition characterized by the extracellular deposition of insoluble, abnormal amyloid fibrils in various body tissues. It is generally categorized into 2 forms - localized and systemic - with a wide range of signs and symptoms. This case report discusses the localized amyloidosis involvement of the oral cavity and its treatment. CASE REPORT A 65-year-old woman presented to the oral medicine clinic reporting painless tongue enlargement, which has been slowly progressing over several years, leading to difficulty in tongue movement, eating, and swallowing. Ex

Pathology Competencies in Medical Education and Educational Cases: Update 2023.

Pathology is a core component of medical school curricula because understanding the pathogenesis of the disease is foundational both for diagnostic efficiency and optimal use of ancillary resources in patient care. The Pathology Competencies for Medical Education (PCME) were developed as a national resource of expectations of pathology knowledge for medical students. The PCME are composed of three competencies: disease mechanisms and processes, organ system pathology, and diagnostic pathology and therapeutic pathology. The learning goals and learning objectives of the PCME that were first publ