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Spotlight on ixazomib: potential in the treatment of multiple myeloma.

Despite the significant therapeutic advances achieved with proteasome inhibitors (PIs) such as bortezomib and carfilzomib in prolonging the survival of patients with multiple myeloma, the development of drug resistance, peripheral neuropathy, and pharmacokinetic limitations continue to pose major challenges when using these compounds. Ixazomib is a second-generation PI with improved activity over other PIs. Unlike bortezomib and carfilzomib, which are administered by injection, ixazomib is the first oral PI approved by US Food and Drug Administration. This review discusses the biochemical prop

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… The most common drug-related AEs included nausea (42%), thrombocytopenia (42%), fatigue (40%), skin and subcutaneous tissue disorders (40%), vomiting (25%), diarrhea (23%), pyrexia (20%), neutropenia (18%), PN (12%), and chills (10%). …

Predicting pneumonia mortality using CURB-65, PSI, and patient characteristics in patients presenting to the emergency department of a comprehensive cancer center.

The prognostic accuracy of the CURB-65 criteria and pneumonia severity index (PSI) in immunocompromised cancer patients with pneumonia is unknown. We sought to determine whether CURB-65 and PSI predict 28-day mortality in cancer patients with pneumonia, and identify other factors that predispose cancer patients with pneumonia to a high mortality risk. We assessed sensitivities, specificities, predictive values, and areas under the receiver operating curve area under the curve (AUC) of the CURB-65 and PSI in predicting the 28-day mortality of cancer patients presenting to our institution's emer

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… Patients were considered to have pneumonia if they had symptoms of an acute lower respiratory tract illness (e.g., coughing) with or without sputum production, or a focal chest sign at auscultation that could be accompanied by systemic symptoms such as fever or chills, and confirmed by the presence of …

Carfilzomib in multiple myeloma patients with renal impairment: pharmacokinetics and safety.

This phase 2 study assessed the safety, pharmacokinetics, pharmacodynamics and efficacy of carfilzomib, a selective proteasome inhibitor, in patients with multiple myeloma and varying degrees of renal impairment, including patients on chronic hemodialysis. Patients were grouped by creatinine clearance: >80 ml/min, 50-80 ml/min, 30-49 ml/min, <30 ml/min and chronic hemodialysis. Carfilzomib was administered on days 1, 2, 8, 9, 15 and 16 in 28-day cycles: 15 mg/m(2) (Cycle 1), 20 mg/m(2) (Cycle 2) and 27 mg/m(2) (Cycles 3+). There were no differences in carfilzomib clearance or exposure among pa

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… On the basis of findings from earlier phase 1 and phase 2 studies, 9 , 14 dexamethasone 4 mg was administered before carfilzomib dosing during Cycle 1 and could be continued in subsequent cycles if treatment-related fever, chills, and/or dyspnea were observed. …

Up-regulation of bone marrow stromal protein 2 (BST2) in breast cancer with bone metastasis.

BackgroundBone metastases are frequent complications of breast cancer. Recent literature implicates multiple chemokines in the formation of bone metastases in breast cancer. However, the molecular mechanism of metastatic bone disease in breast cancer remains unknown. We have recently made the novel observation of the BST2 protein expression in human breast cancer cell lines. The purpose of our present study is to investigate the expression and the role of BST2 in bone metastatic breast cancer.MethodscDNA microarray analysis was used to compare the BST2 gene expression between a metastatic to b

Abstracts from the 37th Annual Meeting of the Society of General Internal Medicine, 2014, San Diego, CA, USA.

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Recent clinical researches and technological development in TIL therapy.

Tumor-infiltrating lymphocyte (TIL) therapy represents a groundbreaking advancement in the solid cancer treatment, offering new hope to patients and their families with high response rates and long overall survival. TIL therapy involves extracting immune cells from a patient's tumor tissue, expanding them ex vivo, and infusing them back into the patient to target and eliminate cancer cells. This revolutionary approach harnesses the power of the immune system to combat cancers, ushering in a new era of T cell-based therapies along with CAR-T and TCR-therapies. In this comprehensive review, we a

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… Administration may lead to transient dyspnea, chills, and fever immediately following infusion [ 22 ]. … IL-2-related reactions : Patients may experience fever, chills, or hypotension during or shortly after the TIL infusion due to IL-2 toxicity [ 24 – 28 ]. These reactions are usually manageable with supportive care and symptomatic treatment. …

Hematology

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… petechiae, subacute combined degeneration of the cord (B12 deficiency affecting dorsal columns and lateral corticospinal tracts), peripheral neuropathy Investigations Basic labs —CBCD, peripheral smear, reticulocyte count, vitamin B12, RBC folate, TSH, AST, ALT, ALP, bilirubin, INR, PTT Special S chilling … Fever, chills | Antihistamine ( diphenhydramine 50 mg IV ×1 dose), acetaminophen Anaphylaxis | Recipient Ab against donor IgA, 1/40,000 | Immediate. ↓ BP, bronchospasm, no fever | Stop transfusion, epinephrine, corticosteroids Urticaria | Recipient IgE against donor antigens, 1/100 plasma-containing …

The Significant Role of RUNX2 Expression in Women with Metastatic Breast Cancer.

ObjectiveBreast cancer (BC) is one of the most common malignancies with second ranks among the causes of tumor-associated mortality in females. Since the overexpression of RUNX2 gene were reported in the development of different malignancies. The present investigation was aimed to find its correlation with prognostic factors viz, tumor grade and stage in the breast cancer patients.MethodsThis study, examined the expression level changes of RUNX2 genes with the Real-time PCR and compared the results with various databases and previous research results, to understand the existence of differences

Feasibility and patient reported tolerance of cryotherapy with Cooral mouth cooling device in patients undergoing radiation therapy (CooRay): a pilot study.

BackgroundRadiation-induced oral mucositis (RIOM) is a major side-effect of (chemo)radiation (CRT) of patients with head and neck cancer (HNC). This study tries to establish a novel cryotherapy (CyT) method using a mouth care device (MCD; Cooral®, BrainCool AB, Lund, Sweden) to prevent RIOM.MethodsPatients were non-randomly assigned to use the MCD after every radiotherapy session for 30-60 minutes. Subjects were asked to answer daily questionnaires assessing tolerability of the intervention. Mucositis was assessed at baseline, once weekly and at weeks 1/3/6 after CRT. The primary endpoint was

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… However, these have downsides such as chills, numbness, taste disturbance, headache or teeth sensations. In addition, it remains uncertain if all regions of the oral cavity are cooled equally. Moreover, a continuous supply of ice chips is necessary during treatments. …

Increasing Gram-Negative Catheter-Related Bloodstream Infection in Cancer Patients.

Background: We aimed to assess the incidence, etiology and outcomes of catheter-related bloodstream infection (CRBSI) in onco-hematological patients, to assess the differences between patients with hematological malignancies (HMs) and solid tumors (STs) and to identify the risk factors for Gram-negative (GN) CRBSI. Methods: All consecutive episodes of BSI in adult cancer patients were prospectively collected (2006-2020). The etiology of CRBSI was analyzed in three different 5-year periods. Risk factors for GN CRBSI were assessed in the whole cohort and separately in patients with HMs and STs.

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… Definitions CRBSI was defined according to the guidelines from the Infectious Disease Society of America (IDSA) [ 11 ]: Bacteremia or fungemia in a patient with an intravascular device and ≥1 positive blood culture result obtained from the peripheral vein, clinical manifestations of infection (e.g., fever, chills …

Bloodstream Infection and Endocarditis Caused by Staphylococcus aureus in Patients with Cancer: A Multicenter Cohort Study.

IntroductionIn a large cohort of patients with Staphylococcus aureus bloodstream infection (SABSI), we aimed to analyze the incidence and risk factors for infective endocarditis (IE) among patients with active cancer (PAC) in comparison with those without cancer (PWC).MethodsMulticenter cohort study of patients with SABSI admitted to two tertiary care hospitals, from 2011 to 2019. PAC were defined as those with an active solid organ cancer or hematological malignancies. SABSI and S. aureus IE were compared between PAC and PWC.ResultsAmong 978 episodes of SABSI, 217 (22.2%) occurred in PAC. PAC

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… Definitions SABSI was defined as at least one positive blood culture obtained from a patient with clinical signs and symptoms of infection (namely fever, chills, malaise, specific signs or symptoms of infection, e.g., phlebitis, cellulitis, septic emboli). …

Daratumumab Monotherapy for Relapsed or Refractory Multiple Myeloma: Results of an Early Access Treatment Protocol in Europe and Russia.

INTRODUCTION: Daratumumab is a human IgGκ monoclonal antibody targeting CD38. Despite the demonstrated benefit of daratumumab in multiple myeloma, not all patients have access to commercially available daratumumab. Here we report a pooled analysis of patients from the UK, Spain, Italy, and Russia enrolled in an open-label, early access treatment protocol (EAP) that provided daratumumab (16 mg/kg) monotherapy to patients with heavily pre-treated relapsed or refractory multiple myeloma (RRMM). METHODS: Intravenous daratumumab 16 mg/kg was administered to patients who had received ≥ 3 prior line

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… Table 4 Most common (> 3% of patients) infusion-related reactions | Daratumumab ( N = 293) Any grade | Grade 3/4 Patients with IRR, n (%) | 132 (45.1) | 10 (3.4) Dyspnea | 26 (8.9) | 3 (1.0) Nasal congestion | 26 (8.9) | 0 Cough | 15 (5.1) | 0 Chills | 13 (4.4) | 0 Nausea | 13 (4.4) | 0 Hypertension …

Beyond CAR T-Cell Therapy: Continued Monitoring and Management of Complications.

Chimeric antigen receptor (CAR) T-cell therapy has recently emerged as a groundbreaking treatment for CD19-expressing hematologic malignancies and received rapid approval by the U.S. Food & Drug Administration. Tisagenlecleucel and axicabtagene ciloleucel are now widely available at CAR T-cell therapy centers around the United States. Many patients have achieved complete response or remission despite failing multiple previous lines of therapy, but some patients endure the severe risks of cytokine release syndrome, neurotoxicity, and other immunologic effects. As more patients receive this ther

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… Beyond these two major toxicities, other adverse reactions for both products include fever, hypotension, tachycardia, fatigue, encephalopathy, headache, tremors, chills, anorexia, diarrhea, nausea, vomiting, constipation, hypoxia, febrile neutropenia, hypogammaglobulinemia, infection, cough, dizziness …

Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine Among Adults Aged ≥65 Years: Updated Recommendations of the Advisory Committee on Immunization Practices.

Two pneumococcal vaccines are currently licensed for use in adults in the United States: a 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Pfizer, Inc.]) and a 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Pneumovax 23, Merck and Co., Inc.]). In 2014, the Advisory Committee on Immunization Practices (ACIP)* recommended routine use of PCV13 in series with PPSV23 for all adults aged ≥65 years based on demonstrated PCV13 safety and efficacy against PCV13-type pneumonia among adults aged ≥65 years (1). At that time, ACIP recognized that there would be a need to reevaluate thi

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… Common reported PCV13-associated adverse reactions included pain, redness, and swelling at the injection site, limitation of movement of the arm in which the injection was given, fatigue, headache, chills, decreased appetite, generalized muscle pain, and joint pain ( 21 ). …

Hypercalcemia of Malignancy: An Emergency Medicine Simulation.

Hypercalcemia is a poor prognostic factor associated with malignancy. The signs and symptoms of hypercalcemia that the patients present to the emergency department are vague and often overlap with the general symptoms of cancer itself or the adverse effects of the chemotherapy. Given that the development of hypercalcemia of malignancy can present with imminent danger to the patient and is a treatable condition, emergency physicians should know how to recognize and treat it. It also marks a time at which discussions regarding plans of care should be initiated with the patients. In this report,

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… Review of systems | General – weight loss (~5-10 lbs over past few weeks), lethargic, decreased appetite, no fever/chills; eyes – no visual changes; ears, nose, throat – no hearing changes, no sore throat; cardiovascular – no chest pain, no palpitations, no shortness of breath, no peripheral edema; respiratory …

Denosumab, a RANK ligand inhibitor, for the management of bone loss in cancer patients.

Bone loss is a common side effect of cancer treatments, especially antihormonal treatments used in the treatment of breast and prostate cancer. Denosumab is a monoclonal antibody given subcutaneously that inhibits osteoclast activity by targeting the RANK ligand. It is effective in settings ranging from preventing skeletal-related complications in cancer patients with metastatic disease to increasing bone mineral density in patients with osteoporosis. In cancer patients with early stage disease, denosumab can attenuate bone loss from antihormonal treatments, and in prostate cancer, may reduce

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… An acute phase reaction is a classic side effect of intravenous bisphosphonates and is characterized by short-term pyrexia, chills, myalgias, and arthralgias. 53 In the HORIZON trial, where zoledronic acid was given yearly for osteoporosis in postmenopausal women, 31.6% of patients had pyrexia, myalgia …

Design and rationale of FOCUS (PX-171-011): a randomized, open-label, phase 3 study of carfilzomib versus best supportive care regimen in patients with relapsed and refractory multiple myeloma (R/R MM).

BACKGROUND: Carfilzomib is a next-generation proteasome inhibitor with single-agent activity in patients with relapsed and refractory multiple myeloma (R/R MM). In PX-171-003-A1, a single-arm phase 2 study of carfilzomib monotherapy in heavily pretreated patients, the overall response rate was 23.7%, 37% of patients achieved ≥ minimal response and median overall survival (OS) was 15.6 months. Based on this study, carfilzomib was recently approved by the US Food and Drug Administration for the treatment of R/R MM. Herein we describe the trial design and rationale for a phase 3 randomized study,

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… Observation of fever, chills, shortness of breath, and/or rigors in these studies led to a selection of 20 mg/m 2 as the initial dose, as well as inclusion of hydration and concomitant dexamethasone (4-mg predose during the first cycle). …

A population-based study of the clinical course of chronic fatigue syndrome.

BackgroundChronic fatigue syndrome (CFS) presents a challenge for patients, health care providers, and health insurance groups because of its incapacitating nature, unknown cause, and poorly understood prognosis. We conducted a longitudinal population-based study to characterize the clinical course of CFS.MethodsSixty-five CFS subjects were identified from a random-digit-dialing survey of Wichita, Kansas residents and followed for up to 3 years. We evaluated changes in CFS classification (partial or total remission, alternative medical or psychiatric diagnoses), CFS case-defining criteria, wel

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… 67.7 | 50.9* | 53.9 | 58.3 Sensitivity to light | 56.9 | 52.5 | 59.0 | 58.3 Depression | 49.2 | 44.1 | 38.5 | 37.5 Numbness or tingling | 35.9 | 44.8 | 30.8 | 58.3* Shortness of breath | 35.4 | 27.1 | 23.1 | 45.8 Stomach or abdominal pain | 24.6 | 30.5 | 28.2 | 13.0 Diarrhea | 20.0 | 20.3 | 20.5 | 4.2 Chills …

Recombinant Oncolytic Viruses: Hexagonal Warriors in the Field of Solid Tumor Immunotherapy.

In the past decade, research on recombinant oncolytic viral agents in the treatment of solid tumors has evolved from the initial stage of simple genetic engineering to the current stage of multiple pipelines of parallel clinical application and combination therapy. Compared with T-VEC, the classical therapeutic agent that only expresses GM-CSF, which was approved in 2015, most new oncolytic virus designs include diverse gene constructs to reduce toxic effects, enhance multiple antitumor immunity, avoid immune clearance, or enhance tumor targeting. The single route of administration that activa

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… The most common AEs are fatigue (50.3%), chills (48.6%), and pyrexia (42.8%) [ 10 ]. T-VEC remains the sole oncolytic virus therapy approved by the FDA. … The most common AEs were fatigue (32.9%), chills (32.1%), and pyrexia (30.7%). A total of 18 patients had grade ≥ 3 TRAEs [ 45 , 46 ]. …

Oncolytic virus therapy in the elderly: immune frailty, challenges, and perspectives.

With global aging accelerating, cancer incidence among older adults is rapidly increasing. Individuals aged ≥65 years now represent 64% of new cancer cases and 71.3% of cancer-related deaths worldwide. This population exhibits a distinct immune imbalance-driven by tumor-induced immunosuppression, immunosenescence, and inflammaging-which contributes to poor tolerance of standard therapies and suboptimal outcomes with PD-1/PD-L1 inhibitors. As an emerging immunotherapeutic strategy, oncolytic viruses (OVs) selectively infect tumor cells, induce immunogenic cell death (ICD), and activate the cGAS

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… . | ( 20 , 126 , 128 ) Real-world pharmacovigilance signals: SIRS/infectious complications | HSV-1 (T-VEC) is primarily administered intralesionally; systemic symptoms such as fever and chills are common, but post-marketing data indicate risks of sepsis and encephalitis. | FAERS review (Q1 2004–Q3 2023 … , N=1138 reports). | Common signals: fever, flu-like symptoms, chills. …